https://scholars.lib.ntu.edu.tw/handle/123456789/604891
標題: | Stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12)-enhanced angiogenesis of human basal cell carcinoma cells involves ERK1/2-NF-kappaB/interleukin-6 pathway | 作者: | CHIA-YU CHU Cha, Shih-Ting Lin, Wan-Chi Lu, Po-Hsuan CHING-TING TAN Chang, Cheng-Chi BEEN-REN LIN Jee, Shiou-Hwa Kuo, Min-Liang |
關鍵字: | ENDOTHELIAL GROWTH-FACTOR; CHEMOKINE RECEPTOR CXCR4; MICROVESSEL DENSITY; GLIOMA-CELLS; CANCER CELLS; FACTOR-I; EXPRESSION; INTERLEUKIN-6; SKIN; METASTASIS | 公開日期: | 二月-2009 | 出版社: | OXFORD UNIV PRESS | 卷: | 30 | 期: | 2 | 起(迄)頁: | 205 | 來源出版物: | Carcinogenesis | 摘要: | Stromal cell-derived factor 1alpha (SDF-1alpha) (CXCL12) has been observed to enhance tumor angiogenesis. However, the comprehensive role of SDF-1alpha (CXCL12)-CXCR4 interaction, exerted during angiogenesis, has not been well understood. We have previously demonstrated that human basal cell carcinoma (BCC) tissues and a BCC cell line (BCC-1/KMC) had significant expression of CXCR4, whose level was higher in invasive than in the non-invasive BCC types. Here, we observed that human BCC tissues with high expression levels of CXCR4 had higher vascularity. Further, among the 71 BCCs diagnosed between the years 2004-2005, BCCs with high CXCR4 expression had concomitantly higher microvessel density, as compared with those with low CXCR4 expression (P < 0.001). We found that SDF-1alpha induced angiogenic activity in human BCC cells, both in vitro and in vivo. SDF-1alpha significantly upregulated several angiogenesis-associated genes such as interferon-alpha-inducible protein 27, interleukin (IL)-6, bone morphogenetic protein (BMP)-6, SOCS2 and cyclooxygenase 2 (COX)-2 in human BCC cells. Among them, IL-6 was the earliest and highest upregulated gene whose induction was observed within 6 h of the commencement of SDF-1alpha-CXCR4 interaction. The mechanisms behind the SDF-1alpha-induced time and dose-dependent upregulation of messenger RNA expression and protein secretion of IL-6 were investigated. The transcriptional regulation of IL-6 by SDF-1alpha was mediated by phosphorylation of extracellular signal-related kinase 1/2 and activation of the nuclear factor-kappaB complex. The identification of the angiogenic profiles induced through SDF-1alpha-CXCR4 interactions in human BCC cells may contribute further insights into the mechanisms involved in the angiogenic potential of SDF-1alpha (CXCL12). |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/604891 | ISSN: | 0143-3334 | DOI: | 10.1093/carcin/bgn228 |
顯示於: | 醫學系 |
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