RESUMO
OBJECTIVE: The aim of this study was to evaluate the expression of endoglin and its correlation with histopathological and clinical findings in conjunctival nevi. METHODS: The study included archival formalin-fixed, paraffin-embedded tissue sections of 44 patients with conjunctival nevi. Immunohistochemical staining for CD105 had been performed with monoclonal mouse antihuman CD105 antibodies. The intratumoral microvessel density for quantification of tumoral vascularization had been determined by this marker. RESULTS: The expression of CD105 was positive in 30 (68.2%) cases. There was a statistically significant difference in the level of CD105 expression regarding the histological type of nevus (p=0.03) and intralesional cysts status (p=0.02). Spearman's rho (ρ -0.316) revealed a significant negative correlation between the expression of endoglin and the histological type of nevus (p=0.03) and between the expression of endoglin and the presence of intralesional cysts (ρ -0.380, p=0.01). CONCLUSION: This study suggests that endoglin could be a useful diagnostic and prognostic marker in differentiating between benign and malignant melanocytic ocular lesions.
Assuntos
Neoplasias da Túnica Conjuntiva , Cistos , Endoglina , Nevo Pigmentado , Neoplasias Cutâneas , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias da Túnica Conjuntiva/metabolismo , Neoplasias da Túnica Conjuntiva/patologia , Cistos/metabolismo , Endoglina/biossíntese , Humanos , Camundongos , Nevo Pigmentado/metabolismo , Nevo Pigmentado/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Although the diagnosis and treatment of sporadic vestibular schwannoma has improved in recent years, no factors capable of predicting its growth have been identified as yet. Endoglin (CD105) is a proliferation-associated protein expressed in angiogenic endothelial cells, and a potential prognostic indicator for several solid tumors. The aim of the present study was primarily to investigate the expression and role of CD105 in a series of sporadic vestibular nerve schwannomas. In 71 consecutive cases of vestibular schwannoma, vessel cross-sectional area and density were calculated from immunohistochemically assessed CD105 expression using image analysis to correlate them with: (i) tumor dimensions; and (ii) tumor growth rate measured on high-resolution contrast-enhanced MRI (ceMRI). Based on assessments of CD105 expression, a significant positive correlation was identified between vessel cross-sectional area and tumor size at the time of surgery (pâ¯=â¯0.0024), and between vessel density and tumor size (pâ¯=â¯0.013). Vessel cross-sectional area (pâ¯=â¯0.0006) and vessel density (pâ¯=â¯0.003) were significantly greater in tumors measuring ≥10â¯mm in size than in those <10â¯mm. Conversely, when tumor growth rate could be calculated from two or more ceMRI (38 cases), there was no significant correlation between tumor growth rate and cross-sectional vessel area or vessel density as assessed with CD105. Further investigations are needed to ascertain the feasibility of: (i) using circulating endoglin assay to monitor tumor growth; and (ii) targeting neoangiogenesis with anti-endoglin antibodies in sporadic vestibular schwannoma.
Assuntos
Neoplasias dos Nervos Cranianos/patologia , Endoglina/biossíntese , Neovascularização Patológica/patologia , Neurilemoma/patologia , Doenças do Nervo Vestibulococlear/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Endoglina/análise , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The amniotic membrane can be considered as one of the sources of isolation of these cells, since it is found in the fetal maternal interface and has low immunogenicity. Mesenchymal stromal/stem cells (MSCs) have not been identified in canine amniotic membrane (AMC). Therefore, our objective was to isolate, culture, characterize and differentiate cells derived from canine amniotic membrane (AMC) and to verify its immunological and tumorigenic potential. For this, 12 dogs fetuses of each gestational age 32, 43 and 55 days were used, and the isolation and culture of the AMC were performed. We observed that the cells presented fibroblastoid morphology and high confluence even after freezing. We also observed that, when induced, they were able to differentiate into osteogenic, adipogenic, and chondrogenic cells, as well as being CD34- and CD105+. Regarding the immunological markers, we found that IL-1, IL-2, IL-6, IL-10 and MHC II were not expressed, whereas MHC I was expressed. After application of AMC cells in nude mice we can verify that there was no tumor formation. Based on this, we conclude that canine amniotic membrane is a good and accessible source for obtaining MSCs of low immunogenic and tumorigenic potential for veterinary therapeutic applications.
Assuntos
Âmnio , Técnicas de Cultura de Células , Diferenciação Celular , Separação Celular , Células-Tronco Mesenquimais , Âmnio/citologia , Âmnio/metabolismo , Animais , Antígenos CD34/biossíntese , Citocinas/biossíntese , Cães , Endoglina/biossíntese , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismoRESUMO
OBJECTIVE: To investigate expression profiles of survivin and endoglin in patients with hepatic carcinoma. MATERIALS AND METHODS: Cancerous tissues (hepatic carcinoma group) of 48 patients with hepatic carcinoma and adjacent noncancerous hepatic tissues (control group) were used as objects of study. Histopathological staining [hematoxylin & eosin (H&E) staining] was used to study the pathological differences in hepatic tissues between hepatic carcinoma group and control group. Moreover, survivin and endoglin protein expressions in hepatic tissues in hepatic carcinoma group and control group were detected via western blotting. Finally, Statistical Product and Service Solutions 17.0 statistical software was used to analyze the differences in survivin and endoglin expressions in hepatic tissues between hepatic carcinoma group and control group. RESULTS: H&E staining showed that histopathological features in hepatic carcinoma group were significantly different from those in control group. Compared with those in control group, the cell structure in hepatic carcinoma group was damaged, karyopyknosis was obvious, and the hepatic injury was serious. Reverse transcription-polymerase chain reaction showed that survivin and endoglin mRNA expression levels in hepatic carcinoma group were significantly increased compared with those in control group. Besides, immunofluorescence method and western blotting revealed the low expressions of survivin and endoglin proteins in tissues in control group, which were obviously lower than those in hepatic tissues in hepatic carcinoma group. Results of analyses of variance showed that the expressions of survivin and endoglin in normal hepatic tissues and cancerous tissues had statistically significant differences (p < 0.01). Furthermore, expressions of survivin and endoglin were significantly associated with histological grade, tumor size, and tumor, node, metastasis (TNM) stage. CONCLUSION: Elevated expressions of survivin and endoglin are associated with histological grade, tumor size, and TNM stage in patients with hepatic carcinoma, indicating that survivin and endoglin might be involved in the pathogenesis of hepatic carcinoma and therapeutic targeting them might be a novel approach for the treatment of hepatic carcinoma.
Assuntos
Carcinoma Hepatocelular/metabolismo , Endoglina/biossíntese , Neoplasias Hepáticas/metabolismo , Survivina/biossíntese , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Endoglina/genética , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Survivina/genéticaRESUMO
The liver is perfused by both arterial and venous blood, with a resulting abnormal microenvironment selecting for more-aggressive malignancies. Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, the sixth most common cancer globally, and the third leading cause of cancer-related mortality worldwide. HCC is characterized by its hypervascularization. Improving the efficiency of anti-angiogenic treatment and mitigation of anti-angiogenic drug resistance are the top priorities in the development of non-surgical HCC therapies. Endoglin (CD105), a transmembrane glycoprotein, is one of the transforming growth factor ß (TGF-ß) co-receptors. Involvement of that protein in angiogenesis of solid tumours is well documented. Endoglin is a marker of activated endothelial cells (ECs), and is preferentially expressed in the angiogenic endothelium of solid tumours, including HCC. HCC is associated with changes in CD105-positive ECs within and around the tumour. The large spectrum of endoglin effects in the liver is cell-type- and HCC- stage-specific. High expression of endoglin in non-tumour tissue suggests that this microenvironment might play an especially important role in the progression of HCC. Evaluation of tissue expression, as well as serum concentrations of this glycoprotein in HCC, tends to confirm its role as an important biomarker in HCC diagnosis and prognosis. The role of endoglin in liver fibrosis and HCC progression also makes it an attractive therapeutic target. Despite these facts, the exact molecular mechanisms of endoglin functioning in hepatocarcinogenesis are still poorly understood. This review summarizes the current data concerning the role and signalling pathways of endoglin in hepatocellular carcinoma development and progression, and provides an overview of the strategies available for a specific targeting of CD105 in anti-angiogenic therapy in HCC.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma Hepatocelular , Endoglina/biossíntese , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas , Proteínas de Neoplasias/biossíntese , Neovascularização Patológica , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologiaRESUMO
BACKGROUND: Endoglin is a marker of active, proliferating endothelial cells of blood vessels. In many cancers, it is present in both peripheral vessels and vessels located inside the tumor. Endoglin is more specific and sensitive compared to other tumor angiogenesis markers. It is suggested that endoglin can be considered a reliable marker of disease outcome. OBJECTIVE: The aim of the study was to assess the expression of endoglin and to determine its potential usefulness as a complementary molecular marker of endometrial cancer. METHOD: The study included 60 women who underwent hysterectomy: 45 with endometrioid endometrial cancer (study group) and 15 without neoplastic changes (control group). The study group was further divided according to the degree of histological differentiation: G1, 17; G2, 15; and G3, 13. The expression of endoglin was determined immunohistochemically with mouse anti-Endoglin monoclonal antibody. The obtained reactions were evaluated using light microscopy. RESULTS: Analysis of endoglin expression in endothelium showed that it reached 145% of the control. In G2, we observed that the endoglin level decreased and was similar to the control, while in G3 it increased and was even higher than in G1. In cancer cells, endoglin expression increased with the grade of endometrial cancer. CONCLUSION: Endoglin can be considered a valuable complementary molecular marker, allowing to visualize the advancement of the cancer process, including endometrial cancer.
Assuntos
Biomarcadores Tumorais/análise , Endoglina/análise , Neoplasias do Endométrio/metabolismo , Endotélio Vascular/metabolismo , Neovascularização Patológica/metabolismo , Animais , Antígenos CD , Estudos de Casos e Controles , Endoglina/biossíntese , Neoplasias do Endométrio/irrigação sanguínea , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Gradação de Tumores , Neovascularização Patológica/patologia , Receptores de Superfície Celular , Transdução de SinaisRESUMO
AIM: To evaluate bevacizumab for epidural fibrosis (EF) treatment in an experimental rat model using histopathology as well as immunohistochemical staining for CD105 and osteopontin (OPN). MATERIAL AND METHODS: Sixteen Wistar Albino rats underwent either laminectomy alone to induce EF (group I, control) or laminectomy plus local bevacizumab treatment (group II). The degree of EF was compared between groups using the current histopathological grading method as well as immunohistochemistry for CD105 and OPN. In addition, the consistency of EF staging using CD105 and OPN expression was compared to that using histopathology. RESULTS: The grade of EF was significantly lower in group II than in group I based on the fibroblast count and fibrosis density determined using histopathology, as well as by CD105 expression determined using immunohistochemistry. In contrast, OPN expression was not a reliable marker for EF evaluation because it did not show a significant difference between the two groups. CONCLUSION: Bevacizumab prevents EF development as assessed using both histopathology and CD105 expression. CD105 is a potentially reliable marker for the immunohistochemical grading of EF, in contrast to OPN.
Assuntos
Bevacizumab/farmacologia , Biomarcadores/análise , Espaço Epidural/efeitos dos fármacos , Espaço Epidural/patologia , Animais , Endoglina/biossíntese , Fibrose/patologia , Imuno-Histoquímica , Masculino , Osteopontina/biossíntese , Ratos , Ratos WistarRESUMO
Recently studies have demonstrated HGMSCs as ideal candidates for regenerative study. Interestingly we found that HGMSCs derived spheroids are more potent and maintain the properties of stemness convincingly compared to conventional culture methods. During the culture, GMSCs instinctively accumulated into spheroids and display multipotent STRO-1 and Vimentin-positive cells. Reduced phenotypic expression of CD73, CD105, and elevated expression STRO-1 and CD-34. Pluripotent nature of S-GMSCs putatively shown the expression of OCT4A, NANOG, SOX-2, SSEA4, TRA-1-60, and TRA-181. Also, levels of protein are much higher in spheroid than dissociated culture. On endothelial induction, spheroid differentiated and developed a vascular structure with positive expression of CD31 and on neuronal induction showed positivity for TUJ1 and E-Cadherin. Importantly, undifferentiated state of S-GMSCs exhibited significant upregulation of aforementioned pluripotent genes and lack of pro-inflammatory cytokines IL-6 and amplified ARF signal confirming that the spheroids are not teratoma formation. However, higher of CAP1, CP, TGFß, OPN, PPARÉ£, TUJ1, and NESTIN expression observed in spheroids, and minimal expression of the same markers were observed in adherent GMSCs respectively. Ahead of dissociated gingival culture, spheroid provides enhanced viable, pluripotent, and multilineage ability. This study suggested that S-GMSCs increased the chances of therapeutic efficacy in the regenerative applications.
Assuntos
Diferenciação Celular/fisiologia , Gengiva/citologia , Células-Tronco Mesenquimais/citologia , Medicina Regenerativa/métodos , Esferoides Celulares/citologia , 5'-Nucleotidase/biossíntese , Adipogenia/fisiologia , Antígenos CD34/biossíntese , Antígenos de Superfície/metabolismo , Linhagem da Célula , Células Cultivadas , Condrogênese/fisiologia , Endoglina/biossíntese , Proteínas Ligadas por GPI/biossíntese , Humanos , Neurogênese/fisiologia , Osteogênese/fisiologia , Vimentina/metabolismoRESUMO
BACKGROUND: CD105 is recently described as a cancer stem cell (CSC) marker. OBJECTIVE: The present study was aimed to investigate the expression and prognostic significance of the CSC marker CD105 in different histological subtypes of renal cell carcinoma (RCC). METHODS: Expression of CD105 was evaluated using immunohistochemistry in RCC samples on tissue microarrays including clear cell RCCs (ccRCCs), papillary, and chromophobe RCCs. The association between CD105 expression and clinicopathological features as well as survival outcomes was determined. RESULTS: In ccRCC, increased tumoral cytoplasmic and endothelial expression of CD105 were significantly associated with advanced stage, renal vein invasion, and microvascular invasion (MVI). In addition, MVI was associated with a worse overall survival (OS). Moreover, in multivariate analysis tumor stage and nuclear grade were independent prognostic factors for OS both in case of tumoral cytoplasmic and endothelial CD105 expression. Additionally, CD105 expression was found to be a predictor of worse OS in univariate analysis. However, in papillary and chromophobe RCC, no significant association was found between CD105 expression and clinicopathological parameters or prognosis. CONCLUSIONS: We showed that CD105 expression was associated with more aggressive tumor behavior, more advanced disease, and worse prognosis in ccRCC but not in the other RCC subtypes.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Endoglina/biossíntese , Neoplasias Renais/patologia , Células-Tronco Neoplásicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Intervalo Livre de Doença , Endoglina/análise , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: The binary system of oral epithelial dysplasia (OED) has never been investigated with reference to the carcinogenesis-related biomarkers. Hence, Ki67, CD105, and α-SMA immune-expressions were studied in oral potentially malignant disorders (OPMDs) to assess their relationship with the binary OED grading system of World Health Organization. METHODS: The study was carried out on paraffin-embedded tissues of 30 normal oral mucosa (NOM) and 140 OPMD cases. OPMD cases were classified into two groups "no/questionable/hyperkeratosis/mild"=low-risk epithelial dysplasia (LRED) and "moderate or severe"=high-risk epithelial dysplasia (HRED). The immunohistochemistry was carried out to evaluate the expression of Ki67, CD 105, and α-SMA antigen. RESULTS: According to the binary grading system of WHO, 69 (49.28%) cases were LRED, while 71 (50.71%) case showed HRED. There was significant increase in Ki67 labeling index (LI) from NOM to LRED to HRED (P=.000). Similarly, mean vascular density (MVD) also increased significantly from NOM to LRED to HRED (P=.000). The α-SMA expression was significantly higher in HERD compared to LRED and NOM (P=.000). A positive correlation was noted among Ki67 LI, MVD, and α-SMA expressions in NOM, LRED, and HRED (P=.000). CONCLUSION: The expressions of ki67, CD105, and α-SMA markers compliment binary grading system of OED in OPMDS, thus justifying its use in clinical practice.
Assuntos
Actinas/biossíntese , Carcinoma in Situ/metabolismo , Endoglina/biossíntese , Antígeno Ki-67/biossíntese , Neoplasias Bucais/metabolismo , Boca/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Epitélio/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Organização Mundial da Saúde , Adulto JovemRESUMO
Preeclampsia is a disease of pregnancy associated with placental oxidative stress, inflammation and elevated release of anti-angiogenic factors sFlt-1 and soluble endoglin. These placental factors cause generalized maternal endothelial dysfunction. There are no treatments to halt disease progression; delivery is the only cure. Resveratrol modulates pathways involved in inflammation and oxidative stress and may offer a potential therapeutic for preeclampsia. Resveratrol reduced sFlt-1, sFlt-1 e15a and soluble endoglin secretion from primary trophoblasts and HUVECs and reduced mRNA expression of pro-inflammatory molecules NFκB, IL-6 and IL-1ß in trophoblasts. IL-6, IL-1ß and TNFα secretion were also significantly reduced. In HUVECs, resveratrol significantly increased mRNA of anti-oxidant enzymes HO-1, NQO1, GCLC and TXN but did not significantly alter HO-1 protein expression, whilst reducing HO-1 protein in trophoblast. Endothelial dysfunction was induced in HUVECs using TNFα, increasing expression of cell adhesion molecule VCAM1 and adhesion of peripheral blood mononuclear cells, both of which were increased further by resveratrol. In contrast, resveratrol significantly reduced TNFα-induced Endothelin-1 (a vasoconstrictor) and significantly increased the phosphorylation of endothelial nitric oxide synthase (eNOS). In summary, resveratrol decreases secretion of anti-angiogenic factors however its effects on the endothelium are mixed. Overall, it may have potential as a treatment for preeclampsia.
Assuntos
Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Endoglina/antagonistas & inibidores , Endoglina/biossíntese , Resveratrol/farmacologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Antioxidantes/farmacologia , Biomarcadores , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Feminino , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/metabolismo , Gravidez , Resveratrol/uso terapêutico , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismoRESUMO
A soluble form of endoglin (sEng) released into the circulation was suggested to be a direct inducer of endothelial dysfunction, inflammation and contributed to the development of hypertension by interfering with TGF-ß signaling in cardiovascular pathologies. In the present study, we assessed the hypothesis that high sEng level-induced hypertension via a possible sEng interference with TGF-ß signaling pathways may result in inflammatory, structural or fibrotic changes in hearts of Sol-Eng+ mice (mice with high levels of soluble endoglin) fed either chow or high-fat diet. Female Sol-Eng+ mice and their age matched littermates with low plasma levels of sEng were fed either chow or high-fat diet (HFD). Heart samples were subsequently analyzed by histology, qRT-PCR and Western blot analysis. In this study, no differences in myocardial morphology/hypertrophy and possible fibrotic changes between Sol-Eng+ mice and control mice were detected on both chow and HFD. The presence of sEng did not significantly affect the expression of selected members of TGF-ß signaling (membrane endoglin, TGFßRII, ALK-5, ALK-1, Id-1, PAI-1 and activated Smad proteins-pSmad 1,5 and pSmad 2,3), inflammation, heart remodeling (PDGFb, Col1A1) and endothelial dysfunction (VCAM-1, ICAM-1) in the hearts of Sol-Eng+ mice compared to control mice on both chow and high-fat diet. High levels of soluble endoglin did not affect microscopic structure (profibrotic and degenerative cardiomyocyte changes), and specific parts of TGF-ß signaling, endothelial function and inflammation in the heart of Sol-Eng+ mice fed both chow diet or HFD. However, we cannot rule out a possibility that a long-term chronic exposure (9 months and more) to soluble endoglin alone or combined with other cardiovascular risk factors may contribute to alterations of heart function and structure in Sol-Eng+ mice, which is the topic in our lab in ongoing experiments.
Assuntos
Cardiomiopatia Hipertrófica/sangue , Endoglina/genética , Regulação da Expressão Gênica , Hipertensão/sangue , Miocárdio/metabolismo , RNA/genética , Animais , Western Blotting , Cardiomiopatia Hipertrófica/etiologia , Cardiomiopatia Hipertrófica/patologia , Modelos Animais de Doenças , Endoglina/biossíntese , Feminino , Perfilação da Expressão Gênica , Coração , Hipertensão/complicações , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miocárdio/patologia , Estresse Oxidativo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
AIMS: Endoglin is a transmembrane glycoprotein, that plays an important role in regulating endothelium. Proteolytic cleavage of membrane endoglin releases soluble endoglin (sEng), whose increased plasma levels have been detected in diseases related to the cardiovascular system. It was proposed that sEng might damage vascular endothelium, but detailed information about the potential mechanisms involved is not available. Thus, we hypothesized that sEng contributes to endothelial dysfunction, leading to a pro-inflammatory phenotype by a possible modulation of the TGF-ß and/or inflammatory pathways. MAIN METHODS: Human umbilical vein endothelial cells (HUVECs) and Human embryonic kidney cell line (HEK293T) were treated with different sEng concentration and time in order to reveal possible effect on biomarkers of inflammation and TGF-ß signaling. IL6 and NFκB reporter luciferase assays, quantitative real-time PCR analysis, Western blot analysis and immunofluorescence flow cytometry were used. KEY FINDINGS: sEng treatment results in activation of NF-κB/IL-6 expression, increased expression of membrane endoglin and reduced expression of Id-1. On the other hand, no significant effects on other markers of endothelial dysfunction and inflammation, including eNOS, peNOSS1177, VCAM-1, COX-1, COX-2 and ICAM-1 were detected. SIGNIFICANCE: As a conclusion, sEng treatment resulted in an activation of NF-κB, IL-6, suggesting activation of pro-inflammatory phenotype in endothelial cells. The precise mechanism of this activation and its consequence remains to be elucidated. A combined treatment of sEng with other cardiovascular risk factors will be necessary in order to reveal whether sEng is not only a biomarker of cardiovascular diseases, but also a protagonist of endothelial dysfunction.
Assuntos
Endoglina/biossíntese , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Interleucina-6/biossíntese , NF-kappa B/biossíntese , Transdução de Sinais , Células HEK293 , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Proteína 1 Inibidora de Diferenciação/biossíntese , SolubilidadeRESUMO
BACKGROUND/AIM: Endoglin (CD105) is a receptor for the transforming growth factor-beta 1 (TGFß1) with crucial role in vascular development and angiogenesis. Additionally, vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival for several cancer types. These molecules have been shown to be useful markers for identifying proliferating endothelium involved in tumor angiogenesis, especially in patients with cancer at risk of developing metastases. The aim of this study was to evaluate the relationship between VEGF and endoglin expression in an experimental model of colorectal cancer, as well as to investigate the effect of cyclooxygenase-2 (COX2) inhibitors on tumor development incidence. MATERIALS AND METHODS: Colon cancer was induced with 1,2-dimethylhydrazine dihydrochloride (DMH). Celecoxib and diclofenac treatment was started simultaneously with DMH induction. Endoglin protein expression was performed using western blot analysis. VEGF plasma concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: In histopathological evaluations, no pathological change was observed in control rats, while adenocarcinoma (62.5%), dysplasia (31.25%) and inflammation (6.25%) were detected in the group given DMH. In treatment groups, a marked decrease was observed in adenocarcinoma rate. Expression of endoglin protein was significantly elevated in the DMH group compared to controls (p<0.001). No statistically significant difference was noted between treatment groups and DMH group regarding endoglin expression but a decrease was detected in the celecoxib-treated groups. CONCLUSION: It was confirmed by histopathology and western blotting that COX2 inhibitors, particularly celecoxib, decrease the rate of disease and slow-down progression of existing CRC. These data show that endoglin expression may have an important role in tumor angiogenesis and predict of tumor invasion.
Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias Colorretais/genética , Endoglina/biossíntese , Neoplasias Experimentais/genética , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Biomarcadores Tumorais/genética , Celecoxib/administração & dosagem , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Diclofenaco/administração & dosagem , Endoglina/genética , Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Imidazóis/toxicidade , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Prognóstico , Ratos , Fator de Crescimento Transformador beta1/biossíntese , Fator de Crescimento Transformador beta1/genética , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Skin dermis includes various types of multipotent stromal cells (MSCs) and a subpopulation of dermal fibroblasts that exhibit the ability to differentiate. However, characterization of this dermal fibroblast subtype remains less understood. In this study, we isolated dermal cells from the skin of newborn C57/B6 mice and investigated their characteristics. Isolated murine dermal cells exhibited a fibroblast phenotype as judged by accepted criteria including a lack of MSC-related antigens and the differentiation potential of MSCs, and the positive expression of fibroblast markers. A comparative analysis demonstrated that CD73(-) CD105(+) but not CD73(-) CD105(-) dermal fibroblasts exhibited some of the functional properties of MSCs. Furthermore, the multipotent phenotype of CD73(-) CD105(+) cells was diminished by treatment of CD105 siRNA and shRNA, indicating that CD105 expression was critical for the retention of differentiation potential of those cells. Overall, these results suggest that CD73(-) CD105(+) cells are a distinct subset of dermal fibroblasts with multipotency and that their surface antigens could help to classify this subpopulation. These cells may contribute to the regeneration of damaged tissue.
Assuntos
5'-Nucleotidase/biossíntese , Derme/citologia , Endoglina/biossíntese , Fibroblastos/metabolismo , 5'-Nucleotidase/imunologia , 5'-Nucleotidase/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Superfície/imunologia , Antígenos de Superfície/metabolismo , Biomarcadores/metabolismo , Diferenciação Celular/fisiologia , Células Cultivadas , Derme/imunologia , Derme/metabolismo , Endoglina/imunologia , Endoglina/metabolismo , Fibroblastos/citologia , Fibroblastos/imunologia , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Multipotentes/classificação , Células-Tronco Multipotentes/metabolismo , Pele/citologia , Pele/imunologia , Pele/metabolismoRESUMO
A new type of mesenchymal stem cells (MSCs) that expresses stage-specific embryonic antigen 3 (SSEA-3) and the mesenchymal cell marker CD105 are known as multilineage-differentiating stress-enduring (Muse) cells. Studies have shown that stem cells in suspension cultures are more likely to generate embryoid body-like stem cell spheres and maintain an undifferentiated phenotype and pluripotency. We separated Muse cells derived from human dermal fibroblasts by long-term trypsin incubation (LTT) through suspension cultures in methylcellulose. The Muse cells obtained expressed several pluripotency markers, including Nanog, Oct4, Sox2, and SSEA-3, and could differentiate in vitro into cells of the three germ layers, such as hepatocytes (endodermal), neural cells (ectodermal) and adipocytes, and osteocytes (mesodermal cells). These cells showed a low level of DNA methylation and a high nucleo-cytoplasmic ratio. Our study provides an innovative and exciting platform for exploring the potential cell-based therapy of various human diseases using Muse cells as well as their great possibility for regenerative medicine.
Assuntos
Reprogramação Celular , Fibroblastos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Antígenos de Diferenciação/biossíntese , Antígenos Glicosídicos Associados a Tumores/biossíntese , Endoglina/biossíntese , Fibroblastos/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Mesenquimais/citologia , Antígenos Embrionários Estágio-Específicos/biossínteseRESUMO
Aim Odontogenic myxoma is a benign intraosseous neoplasm of the jaws, with a locally aggressive behavior and a high recurrence rate. CD-105 is a homodimeric cell membrane glycoprotein and is a component of the TGF-ß1 growth factor receptor complex that modulates angiogenesis by regulating the proliferation, differentiation and cellular migration. The aim of this study is to quantify the microvascular density of the odontogenic myxoma based on the expression of CD-105. Materials and Methods The analysis included 18 odontogenic myxoma and 18 dental follicles as controls. A standard immunohistochemical procedure was performed with the CD-105 antibody. Five representative fields (40×) of the odontogenic myxoma and the dental follicles were selected to determine the microvascular density, which was then followed by a descriptive and comparative statistical analysis. Results Dental follicles presented a significantly higher microvascular density compared with odontogenic myxoma (P = .001). The odontogenic myxoma smaller than 3 cm showed a greater microvascular density than those larger than 3 cm in size (P > .05), and the microvascular density was lower in large odontogenic myxomas as compared with the dental follicles (P = .003). Conclusion A weaker expression of CD-105 in odontogenic myxoma might indicate a lower angiogenic activity, suggesting that vascular proliferation has a limited role in the growth mechanisms and in the aggressive behavior of this neoplasm.
Assuntos
Saco Dentário/metabolismo , Endoglina/biossíntese , Mixoma/patologia , Neovascularização Patológica/metabolismo , Tumores Odontogênicos/patologia , Adolescente , Biomarcadores Tumorais/análise , Criança , Endoglina/análise , Feminino , Humanos , Masculino , Mixoma/metabolismo , Tumores Odontogênicos/metabolismo , Adulto JovemRESUMO
Cell cultures isolated from human endometrium by enzyme digestion consisted of highly viable fibroblast-like mesenchymal cells expressing CD90, CD73, and CD105. During passage 1, the cultures contained a small fraction of cytokeratin-7(+) epithelial cells that disappeared by passage 2. The cultures from the endometrium could be induced to adipogenic, osteogenic and chondrogenic differentiation in vitro. These findings suggest that human endometrium is a convenient source of biomaterial for minimally invasive isolation of cultures that exhibit typical morphology and immunophenotypic profile of resident multipotent mesenchymal stromal cells retain high viability in vitro.