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 calcitonin (CT) and CT gene-related peptide (CGRP), the two splice peptide products of the CALC I gene. Normal and hyperplastic C cells are intrafollicular, in contact with the basement membrane (BM) that is maintained around the differentiated tumors. To investigate the relationships between MTC evolution and BM constituents, we examined the modifications induced by laminin-1 and -2 (merosin), two isoforms colocalized in the follicular BM, on three MTC cell lines: murine rMTC 6-23 and CA-77 cells, and human TT cells. Laminin exerted a mitogenic activity on rMTC 6-23 and on TT cells, causing a concurrent decrease in both CT and CGRP mRNA levels and production of the peptides. Conversely, laminin reduced the proliferation rate and enhanced CGRP 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 line. This suggests that laminin could exert opposite effects depending on the stage of tumor evolution.
Lekmine
F
F
Laboratoire d'Endocrinologie Cellulaire et Evolution, Université Paris-Sud, Orsay, France.
Lausson
S
S
Pidoux
E
E
Segond
N
N
Roos
B
B
Treilhou-Lahille
F
F
Jeanne
A
A
D000818:Animals; D002116:Calcitonin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D006801:Humans; D007797:Laminin / Q000494:pharmacology* / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D020033:Protein Isoforms / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D051381:Rats; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D007797:Laminin; D020033:Protein Isoforms; D012333:RNA, Messenger; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide