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OBJECTIVE: Tertiary lymphoid structures (TLSs) provide sites for antigen presentation and activation of lymphocytes, promoting their infiltration; thus, enhancing specific immune responses. The aim of this comparative cross-sectional study was to reveal the characteristics and influence of TLSs in oral lichen planus (OLP) and oral epithelial dysplasia (OED) with lichenoid features. METHODS: Clinical information and samples of 51 OLP and 19 OED with lichenoid features were collected. Immunohistochemistry was performed, and the structures where CD20+ B cells and CD3+ T cells aggregated with peripheral lymph node addressin positive (PNAd+) vessels were defined as TLSs. The results and clinical information were analysed. RESULT: TLS were found in 44 (86.3%) patients with OLP and 19 (100%) patients with OED. The TLS score was higher in OED group (p = 0.023), accompanied by an increased number of PNAd+ vessels. The TLS was significantly correlated with PNAd+ vessels (p = 0.027), CD20+ B (p < 0.001) and CD208+ dendritic cells (p = 0.001). Foxp3+ Treg cells but not CD8+ T cells infiltrated more severely in OED (p = 0.003) and increased when TLS score was high (p = 0.002). CONCLUSIONS: This study revealed the widespread development of TLSs in the OLP and OED. The presence of TLSs showed a close relationship with dysplasia and may increase malignant potency by over-inducing Treg cells.
Assuntos
Líquen Plano Bucal , Erupções Liquenoides , Estruturas Linfoides Terciárias , Humanos , Líquen Plano Bucal/patologia , Estruturas Linfoides Terciárias/patologia , Estudos Transversais , Hiperplasia , Proteínas de MembranaRESUMO
OBJECTIVE: To evaluate the relation between the expression of PD-1, PD-L1, CD3, CD8, Foxp3 and clinicopathological features in patients with oral leukoplakia (OLK) and oral squamous cell carcinomas (OSCC) as well as the malignant outcome in OLK patients, and to study the effect of PD-1 and PD-L1 on immune microenvironment in the progression of oral carcinogenesis. METHODS: We evaluated the expression of PD-1/PD-L1 and composition of CD3+ , CD8+ and Foxp3+ T lymphocytes in OLK and OSCC samples by immunohistochemical (IHC) staining and analyzed their relation with clinical information and malignant transformation in OLK patients. RESULTS: IHC staining demonstrated that the expression of PD-1 was significantly increased in the high-grade OLK group than in the low-grade OLK group, while PD-L1 was detected mainly in OSCC. The expression of CD3, CD8, and Foxp3 was found higher in the high-grade OLK group than in the low-grade OLK group, and the Foxp3+ cells were found more in the OSCC group than in the high-grade OLK group. PD-1 was significantly correlated with CD3 (p < 0.05, R = 0.52), CD8 (p < 0.05, R = 0.46), and Foxp3 (p < 0.05, R = 0.46), and the low PD-1-expression group showed a better malignant-free survival than high PD-1 expression group in the OLK (p < 0.05). CONCLUSION: The PD-1/PD-L1 may induce immune suppression in OLK and accelerate the progress of malignant transformation.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Receptor de Morte Celular Programada 1 , Antígeno B7-H1 , Leucoplasia Oral/patologia , Transformação Celular Neoplásica , Fatores de Transcrição Forkhead , Microambiente TumoralRESUMO
BACKGROUND: Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, have prominent roles in the development of solid tumors as stromal targets. However, the underlying mechanism of CAFs' function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we investigated the role of lysyl oxidase (LOX) expression in CAFs in tumor stromal remodeling and the mechanism of its effect on OSCC progression. METHODS: Multiple immunohistochemistry (IHC) staining was performed to detect the correlation of CAFs and LOX in the stroma of OSCC specimens, as well as the correlation with clinicopathological parameters and prognosis. The expression of LOX in CAFs were detected by RT-qPCR and western blot. The effects of LOX in CAFs on the biological characteristics of OSCC cell line were investigated using CCK-8, wound-healing and transwell assay. CAFs were co-cultured with type I collagen in vitro, and collagen contraction test, microstructure observation and rheometer were used to detect the effect of CAFs on remodeling collagen matrix. Then, collagen with different stiffness were established to investigate the effect of matrix stiffness on the progression of OSCC. Moreover, we used focal adhesion kinase (FAK) phosphorylation inhibitors to explored whether the increase in matrix stiffness promote the progression of OSCC through activating FAK phosphorylation pathway. RESULTS: LOX was colocalized with CAFs in the stroma of OSCC tissues, and its expression was significantly related to the degree of malignant differentiation and poor prognosis in OSCC. LOX was highly expressed in CAFs, and its knockdown impaired the proliferation, migration, invasion and EMT process of OSCC cells. The expression of LOX in CAFs can catalyze collagen crosslinking and increase matrix stiffness. Furthermore, CAFs-derived LOX-mediated increase in collagen stiffness induced morphological changes and promoted invasion and EMT process in OSCC cells by activating FAK phosphorylation pathway. CONCLUSIONS: Our findings suggest that CAFs highly express LOX in the stroma of OSCC and can remodel the matrix collagen microenvironment, and the increase in matrix stiffness mediated by CAFs-derived LOX promotes OSCC development through FAK phosphorylation pathway. Thus, LOX may be a potential target for the early diagnosis and therapeutic treatment of OSCC.
Assuntos
Fibroblastos Associados a Câncer , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Fibroblastos/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Bucais/patologia , Proteína-Lisina 6-Oxidase/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Microambiente TumoralRESUMO
Heat shock factor 1 (HSF1) is highly expressed in various malignancies and is a potential modulator of tumor progression. Emerging evidence suggests that HSF1 activation in stromal cells is closely related to poor patient prognosis. However, the role of HSF1 in oral squamous cell carcinoma (OSCC) remains elusive. We aimed to investigate the function of HSF1 in cancer-associated fibroblasts (CAFs) of the tumor microenvironment (TME) and in tumor development. In the present study, we found that HSF1 was highly expressed in both CAFs and tumor cells, and was significantly correlated with poor prognosis and overall survival. Moreover, HSF1 overexpression in CAFs resulted in a fibroblast-like phenotype of Cal27 cells, induced epithelial-mesenchymal transition (EMT), and promoted proliferation, migration and invasion in Cal27 cells. HSF1 knockdown attenuated features of CAFs and reduced EMT, proliferation, migration and invasion in Cal27 cells. Furthermore, HSF1 in CAFs promoted tumor growth in nude mice. Taken together, these data suggest that HSF1 expression in CAFs drive OSCC progression, and could serve as an independent prognostic marker of patients with OSCC. Thus, HSF1 is a potent mediator of OSCC malignancy.
Assuntos
Fibroblastos Associados a Câncer/metabolismo , Carcinoma de Células Escamosas/patologia , Fatores de Transcrição de Choque Térmico/metabolismo , Neoplasias Bucais/patologia , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Fibroblastos Associados a Câncer/transplante , Carcinoma de Células Escamosas/metabolismo , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Estadiamento de Neoplasias , Transplante de Neoplasias , Prognóstico , Análise de Sobrevida , Microambiente TumoralRESUMO
BACKGROUND: Tissue invasion and metastasis are acquired abilities of cancer and related to the death in oral squamous cell carcinoma (OSCC). Emerging observations indicate that the epithelial-to-mesenchymal transition (EMT) is associated with tumor progression and the generation of cells with cancer stem cells (CSCs) properties. Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) is a cell surface proteinase, which is involved in degrading extracellular matrix components that can promote tumor invasion and cell migration. METHODS: In the current study, we utilized SCC9 cells stably transfected with an empty vector (SCC9-N) or a vector encoding human MT1-MMP (SCC9-M) to study the role of MT1-MMP in EMT development. RESULTS: Upon up-regulation of MT1-MMP, SCC9-M cells underwent EMT, in which they presented a fibroblast-like phenotype and had a decreased expression of epithelial markers (E-cadherin, cytokeratin18 and ß-catenin) and an increased expression of mesenchymal markers (vimentin and fibronectin). We further demonstrated that MT1-MMP-induced morphologic changes increased the level of Twist and ZEB, and were dependent on repressing the transcription of E-cadherin. These activities resulted in low adhesive, high invasive abilities of the SCC9-M cells. Furthermore, MT1-MMP-induced transformed cells exhibited cancer stem cell (CSC)-like characteristics, such as low proliferation, self-renewal ability, resistance to chemotherapeutic drugs and apoptosis, and expression of CSCs surface markers. CONCLUSIONS: In conclusion, our study indicates that overexpression of MT1-MMP induces EMT and results in the acquisition of CSC-like properties in SCC9 cells. Our growing understanding of the mechanism regulating EMT may provide new targets against invasion and metastasis in OSCC.
Assuntos
Carcinoma de Células Escamosas/enzimologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Metaloproteinase 14 da Matriz/metabolismo , Células-Tronco Neoplásicas , Apoptose , Caderinas/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Fibronectinas/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Queratina-18/metabolismo , Proteínas Nucleares/metabolismo , Fenótipo , Fatores de Transcrição/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Vimentina/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco , beta Catenina/metabolismoRESUMO
Local invasiveness and distant metastasis are critical factors that contribute to oral squamous cell carcinoma-related deaths. Increasing evidence has shown that the epithelial to mesenchymal transition (EMT) is involved in cancer progression and is associated with the 'stemness' of cancer cells. Snail is a transcriptional factor that can induce EMT and preserve stem-cell function, which may induce resistance to radio- and chemotherapies in the cells. In the present study, SCC9 cells were transfected with an empty vector or a vector encoding human Snail (SCC9-S). Overexpression of Snail induced SCC9 cells to undergo EMT, in which the cells presented a fibroblast-like appearance, downregulated the epithelial markers E-cadherin and ß-catenin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Furthermore, the induction of EMT promoted cancer stem cell (CSC)-like characteristics in the SCC9-S cells, such as low proliferation, self-renewal, and CSC-like markers expression. These results indicate that overexpression of Snail induces EMT and promotes CSC-like traits in the SCC9 cells. Further understanding the role of Snail in cancer progression may reveal new targets for the prevention or therapy of oral cancers.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Bucais/genética , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição/genética , Caderinas/análise , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Citometria de Fluxo , Vetores Genéticos , Humanos , Microscopia de Fluorescência , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo , Transfecção , Vimentina/análise , beta Catenina/análiseRESUMO
Oral squamous cell carcinoma is a challenging oncology problem. A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined. Using quantitative immunohistochemistry, we examined the expression of vimentin, E-cadherin, and beta-catenin in 83 oral squamous cell carcinoma patients, and the relationships between the expression of these markers and specific clinicopathological features were analysed. The high expression of vimentin was observed in 23 of 43 (53%) tumours from patients who eventually developed a recurrent tumour and was associated with recurrence and death (P<0.001 and <0.001, respectively). The decreased expression of E-cadherin was observed in 36 of 43 (84%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence and death (P<0.001 and <0.001, respectively). Although no correlation between beta-catenin expression in whole-tumour sections and clinicopathological features was observed, decreased beta-catenin expression at the tumour invasive front was closely associated with recurrence and death (P=0.002 and 0.002, respectively). The expression of vimentin and that of E-cadherin were associated with survival and were independent prognostic factors in univariate and multivariate analyses. Our data show that the overexpression of vimentin was closely associated with recurrence and death in oral squamous cell carcinoma patients. The combination of the upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complexes at the tumour invasive front may provide a useful prognostic marker in oral squamous cell carcinoma.
Assuntos
Biomarcadores Tumorais/análise , Caderinas/biossíntese , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/metabolismo , Vimentina/biossíntese , beta Catenina/biossíntese , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento , Regulação para CimaRESUMO
Mounting lines of evidence indicated that the "colony stimulating factor-1 (CSF-1)/tumor-associated macrophage (TAM)" signature plays an important role in the progression, invasion and metastasis of multiple tumors. However, the potential role of CSF-1/TAM in oral squamous cell carcinoma (OSCC) remains largely unknown. In the present study, the expression of CSF-1 from 99 OSCC specimens and its correlation with clinicopathological features and patient outcomes were investigated. Meanwhile, the correlation between CSF-1 expression and TAM infiltration was also explored. To investigate the potential effect of CSF-1 on tumor growth, nude mice were subcutaneously injected with Cal27 cell line and a small molecule inhibitor of CSF-1 (BZL945). The results showed that the high expression rate of CSF-1 (52%) was found in OSCC, and the upregulation of CSF-1 was closely correlated with lymph node metastasis and clinical stage. Additionally, there was a positive correlation between a high CSF-1 level and elevated TAM infiltration. The xenograft model study showed that CSF-1 signal blockade inhibited tumor growth, with a significant synchronous decrease in CSF-1 expression and TAM infiltration. Overall, our findings indicated that CSF-1 plays a crucial role in TAMs-mediated OSCC tumor progression and invasion. The "CSF-1/TAM" signaling axis may serve as a prospective target for anti-tumor therapy of OSCC.
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Inflammation is closely related to oral squamous cell carcinoma (OSCC). However, its mechanism is still obscure. Toll-like receptor 2 (TLR2) plays an important role in oral chronic inflammatory diseases, but the role of TLR2 in OSCC is unclear. Here, we investigated the expression of TLR2 expression in OSCCs and examined the potential role of TLR2 in OSCC through its association with clinicopathological features and patient outcome. We used 4-nitroquinoline 1-oxide (4-NQO) to induce a tongue cancer model in TLR2-/- and wild type (WT) mice. Histological and clinical results both indicated that TLR2 played a protective role in oral tumorigenesis. The results of a cytometric bead array (CBA) indicated that TLR2 deficiency resulted in Th1 and Th2 cytokine abnormalities, especially Th2 abnormalities. Immunohistochemistry also showed that TLR2 deficiency increases the number of tongue-infiltrating M2 macrophages. Overall, our results demonstrated that TLR2 plays an important role in the prevention of oral tumorigenesis and affects the levels of Th2 cytokines and tongue-infiltrating M2 macrophages; therefore, it may be used to prevent the development of oral cancer.
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To simulate extra-cellular matrix, a novel three-dimensional scaffold of polyelectrolyte complex (PEC) hydrogel as an osteoblast carrier was synthesized. First, chitosan, a natural glycosaminoglycan, was modified by phosphorylation to obtain a water-soluble phosphorylated chitosan (P-content: 10.7 mass%). The PEC hydrogel was then formed from equal volumes of 0.173 mass% phosphorylated chitosan in water and 1 mass% chitosan in 1% (V/V) acetic acid solution. Rat osteoblasts were seeded in the hydrogel. The PEC hydrogel had a three-dimensional hierarchically-porous structure and good cytobiocompatibility for osteoblasts in vitro. It is concluded that the PEC hydrogel is a promising material as an osteoblast carrier.
Assuntos
Quitosana/análogos & derivados , Hidrogéis/farmacologia , Osteoblastos/efeitos dos fármacos , Engenharia Tecidual , Animais , Células Imobilizadas , Quitosana/síntese química , Quitosana/química , Quitosana/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Hidrogéis/síntese química , Hidrogéis/química , Teste de Materiais , Osteoblastos/química , RatosRESUMO
OBJECTIVE: To detect the expression of deltaNp63 in human salivary gland tumor and analyze its role in the malignant salivary gland tumors. METHODS: Collecting the samples from 68 cases of pathologically proven salivary gland tumours and investigating the microscopic sections with HE stain and immunohistochemical-SP stain. RESULTS: It was found that the expression of deltaNp63 is gradually increased in the malignant tumours, the myoepithelial cells and the basal cells of the salivary gland tumors are positive, and the expression of deltaNp63 is correlated directly with benign and malignant tumor. CONCLUSION: deltaNp63 plays an important role in salivary gland tumours. deltaNp63 possesses some special activity that is characteristic of oncogene. p63 is a sensitive and highly specific marker of myoepithelial cells in salivary gland tumours and an additional marker for defining myoepithelial histogenesis. p63 is of definite clinical value in falicitating diagnosis and differential diagnosis.
Assuntos
Cistadenocarcinoma/metabolismo , Proteínas de Ligação a DNA/biossíntese , Mioepitelioma/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Transativadores/biossíntese , Proteínas Supressoras de Tumor/biossíntese , Adenoma Pleomorfo/metabolismo , Adenoma Pleomorfo/patologia , Biomarcadores Tumorais/biossíntese , Cistadenocarcinoma/patologia , Humanos , Imuno-Histoquímica , Mioepitelioma/patologia , Neoplasias das Glândulas Salivares/patologia , Fatores de TranscriçãoRESUMO
TRPM2, one member of the transient receptor potential (TRP) protein super-family, is a Ca2+-permeable channel that is activated by oxidative stress and confers susceptibility to cell death. In the human tongue specimens of carcinoma and the tongue carcinoma SCC cell lines, we observed the enhanced expression of TRPM2. By means of the whole-cell electrophysiological recording, the ADPR-induced currents mediated by TRPM2 were recorded in cultured SCC9 cells. Moreover, after H2O2 treatment for 24 hours, the apoptotic number of SCC9 cells was significantly increased. However, the selectively knocked-down TRPM2 with the small interfering RNA technique inhibited the survival and migration of the SCC9 cancer cells, which was independent of the p53-p21 pathway, since the expression of p21 was enhanced after TRPM2 knockdown. Furthermore, the sub-cellular localization of TRPM2 was remarkably different between cancerous and non-cancerous cells. A significant amount of the TRPM2 proteins were located in the nuclei in cancer cells. All these data suggest that TRPM2 is essential for the survival and migration of SCC cancer cells and may be a potential target for the selective treatment of tongue cancer.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Clusterina/metabolismo , Neoplasias Bucais/metabolismo , Adenosina Difosfato Ribose/farmacologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Peróxido de Hidrogênio/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Estresse Oxidativo/efeitos dos fármacos , Frações Subcelulares/metabolismo , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
BACKGROUND: Both tumor-associated macrophages (TAMs) and the epithelial to mesenchymal transition (EMT) of cancer cells play key roles in promoting tumor progression. However, whether TAMs could induce EMT in the progression of oral squamous cell carcinoma (OSCC) remains undefined. RESULTS: Here we detected the expression of macrophages markers CD68 and CD163, epithelial marker E-cadherin and mesenchymal marker vimentin in 127 OSCC patients by using semi-quantitative immunohistochemistry. CD68 and CD163 expression was not confined to the infiltrating TAMs, but also detected in cancer cells. The high number of CD68-positive macrophages was correlated with poor overall survival. Meanwhile, the expression of CD163 both in macrophages and in cancer cells was associated with poor overall survival and had a significant prognostic impact in OSCC. Importantly, the expression of CD163 in cancer cells had a significant relationship with E-cadherin and vimentin. Furthermore, the incubation of TAMs conditioned medium resulted in a fibroblast-like appearance of cancer cells (HN4, HN6 and SCC9) together with the decreased/increased expression of E-cadherin/ vimentin, which were correlated with the enhanced ability of migration and invasion. CONCLUSIONS: Our results indicate that TAMs could promote the EMT of cancer cells, thereby leading to the progression of oral cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Transição Epitelial-Mesenquimal , Macrófagos/patologia , Neoplasias Bucais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores Tumorais/genética , Caderinas/genética , Caderinas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Meios de Cultivo Condicionados/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Prognóstico , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Análise de Sobrevida , Células Tumorais Cultivadas , Vimentina/genética , Vimentina/metabolismoRESUMO
The inflammatory tumor microenvironment has been identified to play a pivotal role in tumor development and metastasis. Tumor necrosis factor-α (TNF-α) is one of the key cytokines that regulate the inflammatory processes in tumor promotion. In the current study, we treated three oral squamous cell carcinoma (OSCC) cell lines with TNF-α to study its role in inflammation-induced tumor progression. Here we show that TNF-α induces stabilization of the transcriptional repressor Snail and activates NF-κB pathway in the three OSCC cell lines. These activities resulted in the increased motility and invasiveness of three OSCC cell lines. In addition, upon dealing with TNF-α for the indicated time, three OSCC cell lines underwent epithelial-to-mesenchymal transition (EMT), in which they presented a fibroblast-like phenotype and had a decreased expression of epithelial marker (E-cadherin) and an increased expression of mesenchymal marker (vimentin). We further demonstrated that TNF-α can up-regulate the expression of Id2 while inducing an EMT in oral cancer cells. Finally, we showed that Id2 interacted with Snail which may constrain Snail-dependent suppression of E-cadherin. In conclusion, our study indicates that TNF-α induces Snail stabilization is dependent on the activation of NF-κB pathway and results in increasing cell invasion and migration in OSCC cells. Id2 may contribute to regulate the function of Snail during TNF-α-mediated EMT in OSCC. These findings have significant implications for inflammation-induced tumor promotion in OSCC.
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A novel biomimetic mineralization system was designed to induce a layer of hydroxyapatite on a demineralized dentin surface. This system was constructed as follows. A layer of 0.5% agarose gel containing 0.26M Na(2) HPO(4) was used to cover acid-etched dentin slices, followed by a layer of agarose gel without phosphate ions. Then a neutral 0.13M CaCl(2) solution was added onto the ion-free gel surface. The mineralization system (dentin-agarose gel containing phosphate ions-CaCl(2) solution) was kept in a water bath at 37°C, and the gel and CaCl(2) solution were replaced at various intervals. The results showed that the deposited hydroxyapatite crystals densely packed to each other, completely covered the dentin surface, and occluded the dentinal tubules after 10 days of biomimetic mineralization in vitro. Therefore, this method may provide the experimental basis for dentin remineralization and for a new method to treat dentin hypersensitivity and dental caries.
Assuntos
Materiais Biomiméticos/síntese química , Dentina/química , Durapatita/síntese química , Sefarose/química , Materiais Biomiméticos/química , Materiais Biomiméticos/uso terapêutico , Cárie Dentária/terapia , Sensibilidade da Dentina/terapia , Durapatita/química , Durapatita/uso terapêutico , Géis/química , HumanosRESUMO
OBJECTIVE: To examine the E-cadherin and beta-catenin expression in oral squamous cell carcinoma of tongue (OSCCT) and investigate the relationship of these markers with clinicopathologic features and patient prognosis. METHODS: Quantitative immunohistochemistry analysis was used to examine E-cadherin and beta-catenin expression in lesions of 30 OSCCT patients. The relationship between the expression of E-cadherin and beta-catenin and clinicopathological features was analyzed. RESULTS: The decreased expression of E-cadherin was observed in 19 of 30 (63%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence (P=0.007). The expression of E-cadherin was associated with survival (P=0.018) and an independent prognostic factor in univariate analysis. There was no correlation between the expression level of E-cadherin and sex, age, histological differentiation, tumour size, clinical stage, or lymph node metastasis. The high expression of beta-catenin was observed in 18 of 30 (60%) tumours. No correlation between beta-catenin expression and clinicopathological features was observed. CONCLUSIONS: The absence or reduced expression of E-cadherin was closely associated with recurrence and survival in OSCCT patients. The aberrant expression of E-cadherin may provide a useful prognostic marker in OSCCT.
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Caderinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias da Língua/metabolismo , beta Catenina/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Taxa de Sobrevida , Neoplasias da Língua/patologia , Neoplasias da Língua/cirurgiaRESUMO
AIM: The purpose of this study is to compare the effects of the two clutches on recording the condylar movement. METHODOLOGY: Ten subjects (6 women, 4 men; mean age 25.4 years) participated in the study. The mandibular movement, sagittal condylar inclination angle, and transversal condylar inclination angle of each subject were recorded with the CADIAX using the two clutches, respectively. The characteristics of the tracings of the protrusion, opening, and mediotrusion were analyzed with the t-test statistics at a = 0.05 level. The Kappa values were calculated for an assessment of the congruence of the tracings. RESULTS: The results showed that the contour, direction, and dimension of the tracings in the two clutches were approximately same, but the tracings determined by the functional occlusal clutch were more regular and congruent. In the group segment recorded with the tray clutch, opening/closing paths of one subject showed crossed and time curves of three subjects appeared peak-like changes of velocity, but none were statistically different (P>0.05). CONCLUSION: The research suggests that the functional occlusal clutch should be preferred in the evaluation of the mandibular function, as the tracings with the tray clutch are more likely to produce false positive results.
Assuntos
Diagnóstico por Computador/instrumentação , Côndilo Mandibular/fisiologia , Articulação Temporomandibular/fisiologia , Adulto , Oclusão Dentária , Feminino , Humanos , Registro da Relação Maxilomandibular/instrumentação , Masculino , MovimentoRESUMO
During tooth development, cranial neural crest (CNC) cells represent a population of pluripotent stem cells that give rise to various dental tissues. This study aimed to investigate whether CNC cells could differentiate into odontoblast-like cells by in vitro induction. CNC cells were isolated from explants of cranial neural tubes and cultured in serum-free Dulbecco's modified Eagle's medium (DMEM)/F12 medium which contained fibroblast growth factor 8 (FGF8) and dentin non-collagen proteins (DNCP). The initiation of controlled differentiation was determined using histological assays, and the expression of specific gene phenotypes was detected using immunocytochemical staining and reverse transcription--polymerase chain reaction (RT--PCR). The first branchial arch phenotype of the CNC cells demonstrated negative Hoxa2 expression and positive vimentin expression in the presence of 100 ng/ml FGF8. Following DNCP induction, the CNC cells became bipolar, demonstrated high alkaline phosphatase (ALP) activity, and formed mineralized nodules. In addition, the expression of DSPP, DMP1, and collagen type I confirmed the odontoblast phenotype. The results indicate that the tissue-specific cellular differentiation (odontoblast-like cells) of early-stage embryonic-derived cells (such as CNC cells) can be induced by adult extracellular matrix proteins (such as DNCP). CNC cells may be used as a valuable cell model for research on dental tissue differentiation and regeneration.
Assuntos
Proteínas da Matriz Extracelular/farmacologia , Fator 8 de Crescimento de Fibroblasto/farmacologia , Crista Neural/citologia , Odontoblastos/citologia , Células-Tronco Pluripotentes/citologia , Crânio/embriologia , Animais , Calcificação Fisiológica , Diferenciação Celular , Meios de Cultura Livres de Soro , Dentina/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Crista Neural/efeitos dos fármacos , Crista Neural/metabolismo , Células-Tronco Pluripotentes/efeitos dos fármacos , Células-Tronco Pluripotentes/metabolismo , Crânio/citologiaRESUMO
OBJECTIVE: To study the expression of P63 in human salivary gland development and the existing of salivary gland stem cells. METHODS: 24 embryonic salivary gland samples in different stage, 10 normal salivary gland samples were collected. HE-stained and immunochemistry stain were used. RESULTS: It could be seen on the HE-stained sections that the epithelial buds proliferated to form the epithelial branches and duct systems, finally the terminal cells differentiated into ductal, myoepithelial and acinous. During the development of salivary gland, the expression of P63 was gradually reduced. In normal adult salivary gland samples, the positive cell interspersed in the basal layer of intercalated duct, secretory duct and excretory duct. CONCLUSION: P63 plays an important role in human salivary gland development. The result of our experiment shows the distributive characteristic of salivary gland stem cells, which exist abroad in bud stage, but decrease and only exist in the basal layer of ducts in normal adult salivary gland.
Assuntos
Diferenciação Celular , Glândulas Salivares , Adulto , HumanosRESUMO
OBJECTIVE: To investigate the regulatory mechanism of parathyroid hormone-related protein (PTHrP) in proliferation and differentiation of chondrocytes of condyle in fetal mouse. METHODS: Chondrocytes of condyle in fetal mouse were separated and cultured in vitro, the influence of PTHrP on proliferation and differentiation was observed. RESULTS: After two weeks' culture in 0.01 nmol/L, 0.1 nmol/L, 1 nmol/L, 10 nmol/L human PTHrP, there was significant difference in the number of cartilage nodule formed between experiment group and control group (P<0.05), and there was no significant difference in 0.01 nmol/L group (P>0.05). Alkaline phosphatase (ALP) activity was significantly intensified in experiment group and control group (P<0.05). Meanwhile, it was found that this function of promotion was lessened after anti-PTHR antibody used. CONCLUSION: It can be seen that PTHrP, via its receptor, can promote proliferation and differentiation of chondrocytes of condyle, which resemble its modulation mechanism in epiphyseal growth plate cartilage intramembrane in mandibule.