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1.
Clin. transl. oncol. (Print) ; 15(7): 541-547, jul. 2013. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-127466

RESUMO

OBJECTIVE: As a small heavily glycosylated mucin-like glycosyl-phosphatidylinositol-anchored cell surface protein, CD24 plays an important role in carcinogenesis of various human malignancies. However, its involvement in osteosarcoma is still unclear. The aim of this study was to investigate the expression pattern and the clinical significance of CD24 in human osteosarcoma. METHODS: CD24 mRNA and protein expression levels were, respectively, detected by RT-PCR and Western blot assays using 30 pairs of osteosarcoma and noncancerous bone tissues. Then, immunohistochemistry was performed to analyze the association of CD24 expression in 166 osteosarcoma tissues with clinicopathological factors or survival of patients. RESULTS: CD24 expression at mRNA and protein levels were both significantly higher in osteosarcoma tissues than those in corresponding noncancerous bone tissues (both P < 0.001). In addition, CD24 protein was positively expressed in 129 of 166 (77.7 %) osteosarcoma specimens with a cytoplasmic and membraneous staining, and also increased in the osteosarcoma specimens with advanced clinical stage (P = 0.01) and positive distant metastasis (P = 0.005). The univariate and multivariate analyses showed that osteosarcoma patients with high CD24 expression had poorer overall and disease-free survival, and high CD24 expression was an independent prognostic factor for both overall and disease-free survival. CONCLUSION: The aforementioned findings offer convincing evidence for the first time that the increased expression of CD24 is correlated with tumor ggressiveness and tumor metastasis of osteosarcoma, and this molecule is an independent prognostic marker for osteosarcoma patients (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Antígeno CD24/genética , Neoplasias Ósseas/metabolismo , Osteossarcoma/metabolismo , Antígeno CD24/metabolismo , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Imuno-Histoquímica , Osteossarcoma/diagnóstico , Osteossarcoma/patologia , Prognóstico , RNA Mensageiro/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
2.
Clin. transl. oncol. (Print) ; 15(1): 46-54, ene. 2013. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-126967

RESUMO

BACKGROUND: Recent studies suggest that the relationship between cancer stem cells (CSCs) and the vascular niche may be bidirectional; the niche can support the growth and renewal of CSCs, and CSCs may contribute to the maintenance of the niche. There is little knowledge concerning the role of breast cancer stem cells in promoting tumor angiogenesis. AIM: For human breast cancers, CSCs have been shown to be associated with a CD44+/CD24- phenotype. We investigated the potential activities of CD44+/CD24- breast cancer stem cells in promoting tumor angiogenesis. METHODS: The expression of pro-angiogenic genes was determined by quantitative real-time RT-PCR. Endothelial cell migration assays were employed to evaluate effects of conditioned media from CD44+/CD24- on human umbilical vein endothelial cells. A chorioallantoic membrane (CAM) assay was used to study the potential of CD44+/CD24- cells to promote angiogenesis. RESULTS: In our study, CD44+/CD24- cells expressed elevated levels of pro-angiogenic factors compared with CD44+/CD24+ cells. CD44+/CD24- cell-conditioned media significantly increased endothelial cell migration. Breast cancer cell lines enriched with CD44+/CD24- cells were more pro-angiogenic in the CAM assay than hose lacking a CD44+/CD24- subpopulation. CD44+/CD24- cells sorted from MCF-7 cell lines were more pro-angiogenic in a CAM assay than CD44+/CD24+ cells. Furthermore, the VEGF concentration was significantly higher in CD44+/CD24- cell-conditioned media than in CD44+/CD24+ cell-conditioned media. The pro-angiogenic effect of CD44+/CD24- cells on endothelial cells was abolished by bevacizumab. CONCLUSION: Our findings demonstrate that CD44+/CD24- breast cancer stem cells have substantial pro-angiogenic potential and activity. This provides new insights to explore in the development of targeted therapies (AU)


Assuntos
Humanos , Animais , Feminino , Inibidores da Angiogênese/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Antígeno CD24/metabolismo , Receptores de Hialuronatos/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Embrião de Galinha , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/metabolismo , Células Endoteliais , Células Endoteliais/fisiologia , Células-Tronco Neoplásicas , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia
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