Mangahas Catherine R, dela Cruz Gelo V, Friedman-Jiménez George, Jamal Sumayah
The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA.
J Invest Dermatol. 2005 Aug;125(2):307-11. doi: 10.1111/j.0022-202X.2005.23820.x.
The endothelin pathway plays a critical role in melanoma tumor progression by a variety of mechanisms that enhance tumor cell growth, invasion, and metastasis. Here, we investigate the effect of this pathway on CXC chemokine expression in human melanoma cells and melanocytes. As determined by ELISA, endothelin-1 (ET-1) induces CXCL1 and CXCL8 secretion in three human melanoma cell lines in a concentration-dependent fashion. These responses are mediated by the endothelin-B receptor and are sustained over a 40 h time course. ET-1 does not induce CXCL1 secretion in primary human melanocytes but ET-3, an endothelin isoform, induces a low level of CXCL1 secretion in certain cultures. Neither ET-1 nor ET-3 induces secretion of CXCL8 in primary human melanocytes; thus, this response may be specific for melanocytic cells that have undergone malignant transformation. We have previously demonstrated that ET-1 induces changes in the expression of adhesion molecules in melanoma cells such that invasion and metastasis are favored. This study demonstrates that ET-1 additionally induces secretion of CXC chemokines critical for melanoma metastasis and tumor progression.
内皮素信号通路通过多种促进肿瘤细胞生长、侵袭和转移的机制，在黑色素瘤肿瘤进展中发挥关键作用。在此，我们研究该信号通路对人黑色素瘤细胞和黑素细胞中CXC趋化因子表达的影响。通过酶联免疫吸附测定（ELISA）确定，内皮素-1（ET-1）以浓度依赖的方式诱导三种人黑色素瘤细胞系分泌CXCL1和CXCL8。这些反应由内皮素B受体介导，并在40小时的时间进程中持续存在。ET-1不诱导原代人黑素细胞分泌CXCL1，但内皮素异构体ET-3在某些培养物中诱导低水平的CXCL1分泌。ET-1和ET-3均不诱导原代人黑素细胞分泌CXCL8；因此，这种反应可能对已发生恶性转化的黑素细胞具有特异性。我们之前已经证明，ET-1会诱导黑色素瘤细胞中黏附分子的表达发生变化，从而有利于侵袭和转移。本研究表明，ET-1还会额外诱导对黑色素瘤转移和肿瘤进展至关重要的CXC趋化因子的分泌。
