TY - JOUR
T1 - Endothelin-1 induces CXCL1 and CXCL8 secretion in human melanoma cells
AU - Mangahas, Catherine R
AU - dela Cruz, Gelo V
AU - Friedman-Jiménez, George
AU - Jamal, Sumayah
PY - 2005/8
Y1 - 2005/8
N2 - 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.
AB - 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.
KW - Cell Line, Tumor
KW - Chemokine CXCL1
KW - Chemokines, CXC/metabolism
KW - Dose-Response Relationship, Drug
KW - Endothelin-1/pharmacology
KW - Endothelin-3/pharmacology
KW - Humans
KW - Intercellular Signaling Peptides and Proteins/metabolism
KW - Interleukin-8/metabolism
KW - Melanocytes/cytology
KW - Melanoma/metabolism
KW - Receptor, Endothelin B/metabolism
KW - Skin Neoplasms/metabolism
U2 - 10.1111/j.0022-202X.2005.23820.x
DO - 10.1111/j.0022-202X.2005.23820.x
M3 - Journal article
C2 - 16098041
SN - 0022-202X
VL - 125
SP - 307
EP - 311
JO - The Journal of Investigative Dermatology
JF - The Journal of Investigative Dermatology
IS - 2
ER -