Induction of autocrine factor inhibiting cell motility from murine B16–Bl6 melanoma cells by α-melanocyte stimulating hormone
✍ Scribed by Jun Murata; Koichi Ayukawa; Masaru Ogasawara; Hideomi Watanabe; Ikuo Saiki
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 154 KB
- Volume
- 80
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
We have previously reported that neuropeptide ␣-melanocyte stimulating hormone (␣-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 ␣-MSH. ␣-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, ␣-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, ␣-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration-and timedependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by ␣-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2Ј, 5Ј-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from ␣-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 ␣-MSH-stimulated CM. Our results suggest that ␣-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).