Expression of laminin-2 by normal and neoplastic rat C cells during the development of medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) originates from C cells, which secrete ca lcitonin (CT), their specific marker. C cells are located in contact with t he basement membrane (BM) of the thyroid follicles, which is partly made up of the laminin-2 isoform synthesized by thyrocytes. During oncogenesis, pr oliferation of the C cells, invading the centre of the follicles, leads to a break in their normal contact with the BM. As specific interactions of ce lls with BM components, especially laminins, are important for proliferatio n and differentiation, we investigated the relationships of normal and neop lastic C cells with laminin in the Wag/Rij rat model of human MTC. Immunocy tochemical studies showed a progressive loss of the laminin layer underlyin g the hyperplastic C cell nodules around the large dedifferentiated tumours . The alpha 2, beta 1 and gamma 1 chains of the laminin-2 isoform were synt hesized and secreted by rat MTC 6-23 cell cultures and the tumours induced by subcutaneous injection of these cells. In situ hybridization combined wi th anti-CT immunocytochemistry showed a low expression of alpha 2 mRNA on d ifferentiated C cells and thyrocytes, but an overexpression on immunonegati ve spontaneous MTC and induced intrathyroid tumours. The high level of alph a 2 gene expression, together with tumour dedifferentiation, suggests a rel ationship with malignancy.