SWITCHES IN THE EXPRESSION AND FUNCTION OF PACAP AND VIP RECEPTORS DURING PHENOTYPIC INTERCONVERSION IN HUMAN NEUROBLASTOMA-CELLS

Clonal human neuroblastoma cells SH-IN undergo a very conspicuous phen otypic change in culture. Large substrate-adherent cells with a slow g rowth rate give rise to small cells emerging in focal aggregates and g rowing to high cell densities. This is accompanied by a dramatic switc h in the expression of receptors for the structurally related neuropep tides VIP (vasoactive intestinal polypeptide) and PACAP (pituitary ade nylate cyclase activating polypeptide). Large cells expressed mainly P ACAP-specific receptors that triggered stimulation of intracellular cG MP production. On the other hand, polyvalent VIP/PACAP receptors posit ively coupled to adenylate cyclase were mostly observed in the small c ells. Both neuropeptides stimulated cell proliferation in large and sm all cells. These data, together with the previous demonstration of aut ocrine/paracrine actions of VIP and PACAP in human neuroblastomas, sup port the idea that these neuropeptides may participate in the establis hment of the apparent phenotype in these cancer cells.