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Induction of autocrine factor inhibiting cell motility from murine B16–Bl6 melanoma cells by α‐melanocyte stimulating hormone
Author(s) -
Murata Jun,
Ayukawa Koichi,
Ogasawara Masaru,
Watanabe Hideomi,
Saiki Ikuo
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990315)80:6<889::aid-ijc15>3.0.co;2-m
Subject(s) - motility , autocrine signalling , endocrinology , biology , medicine , secretion , microbiology and biotechnology , receptor , biochemistry
We have previously reported that neuropeptide α‐melanocyte stimulating hormone (α‐MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16–BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by α‐MSH. α‐MSH significantly blocked the autocrine motility factor (AMF)‐enhanced cell motility. However, α‐MSH did neither prevent the secretion of AMF from B16–BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, α‐MSH induced the secretion of the motility inhibitory factor(s) from B16–BL6 cells in a concentration‐ and time‐dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by α‐MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2′, 5′‐dideoxyadenosine (DDA). The motility‐inhibiting activity in conditioned medium (CM) from α‐MSH‐treated B16–BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in α‐MSH‐stimulated CM. Our results suggest that α‐MSH inhibited the motility of B16–BL6 cells through induction of autocrine factor(s). Int. J. Cancer, 80:889–895, 1999. © 1999 Wiley‐Liss, Inc.