Induction of cellular contractions in the human melanoma cell line SK-mel 28 after muscarinic cholinergic stimulation

In a previous immunohistochemical study we observed muscarinic acetylcholin e receptors in primary and metastatic human melanomas, which were not prese nt in normal skin melanocytes. In the present study we demonstrated the end ogenous expression of muscarinic receptors, of choline acetyltransferase an d of cholinesterase activity in the human melanoma cell line SK-mel 28. We tested the effect of muscarinic agonists on cellular movements of the melan oma cells in a perfusion chamber by digital video time-lapse microscopy. Wi thin 3 to 10 min after onset of muscarinic perfusion cell body contractions and retraction of cell processes of more, than 5 mu m occurred in about 30 % of the melanoma cells. The effect disappeared after addition of atropine. The proportion of reacting cells corresponded to the endogenous expression of muscarinic receptors revealed by immunocytochemistry with the monoclona l antibody M35. The experiments indicate the presence of an autocrine musca rinic cholinergic system in the melanoma cells and demonstrate a direct lin k between muscarinic receptors and the contractile apparatus. Melanocytes a re derived from neural crest cells that express cholinesterase activity and muscarinic receptors during their migratory phase in the embryo. Therefore , re-expression of the muscarinic cholinergic system in tumour cells may be involved in invasive growth.