Influence of laminin substratum on cell proliferation and CALC I gene expression in medullary thyroid carcinoma C cell lines

Medullary thyroid carcinoma (MTC) originates from C cells, which secrete ca lcitonin (CT) and CT gene-related peptide (CGRP), the two splice peptide pr oducts of the CALC I gene. Normal and hyperplastic C cells are intrafollicu lar, in contact with the basement membrane (BM) that is maintained around t he differentiated tumors. To investigate the relationships between MTC evol ution and BM constituents, we examined the modifications induced by laminin -l and -2 (merosin), two isoforms colocalized in the follicular BM, on thre e MTC cell lines: murine rMTC 6-23 and CA-77 cells, and human TT cells. Lam inin exerted a mitogenic activity on rMTC 6-23 and on TT cells, causing a c oncurrent decrease in both CT and CGRP mRNA levels and production of the pe ptides. Conversely, laminin reduced the proliferation rate and enhanced CGR P synthesis and secretion in CA-77 cells. This antiproliferative response, which coincides with an increase in differentiation markers, is comparable to that reported in normal cells and also in the neoplastic Caco-2 cell lin e. This suggests that laminin could exert opposite effects depending on the stage of tumor evolution. (C) 1999 Elsevier Science Ireland Ltd. All right s reserved.