Human melanoma cells express functional endothelin-1 receptors.
Current evidence suggests that endothelium-derived factors enhance human melanoma vascular invasion. Therefore, we studied human melanoma cell expression of receptors to the endothelium-derived peptide, endothelin-1 (ET-1), and determined if they respond to ET-1 with proliferation and chemokinesis. Human metastatic melanoma cell lines were found to have specific, saturable, high affinity ET-1 binding. Northern analysis and competitive inhibition studies confirmed that melanoma cells express the ETB receptor isoform. Ten nanomolar ET-1 caused an 8.2 to 25.5-fold increase in intracellular free calcium. ET-1 was found to be a weak mitogen for melanoma cells, however, melanoma cell chemokinesis was significantly increased by ET-1. These data suggest that ET-1 may be involved in providing a chemokinetic and growth factor environment that enhances perivascular proliferation and invasiveness of melanoma cells.
Yohn
J J
JJ
Department of Dermatology, University of Colorado School of Medicine, Boulder.
Smith
C
C
Stevens
T
T
Hoffman
T A
TA
Morelli
J G
JG
Hurt
D L
DL
Yanagisawa
M
M
Kane
M A
MA
Zamora
M R
MR
D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D016232:Endothelins / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008545:Melanoma / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D017466:Receptors, Endothelin / Q000032:analysis* / Q000502:physiology; D014407:Tumor Cells, Cultured
D016232:Endothelins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017466:Receptors, Endothelin; D002118:Calcium