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

Abstract

Medullary thyroid carcinoma (MTC) originates from C cells, which secrete calcitonin (CT), their specific marker. C cells are located in contact with the basement membrane (BM) of the thyroid follicles, which is partly made up of the laminin-2 isoform synthesized by thyrocytes. During oncogenesis, proliferation 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 cells with BM components, especially laminins, are important for proliferation and differentiation, we investigated the relationships of normal and neoplastic C cells with laminin in the Wag/Rij rat model of human MTC. Immunocytochemical studies showed a progressive loss of the laminin layer underlying the hyperplastic C cell nodules around the large dedifferentiated tumours. The alpha2, beta1 and gamma1 chains of the laminin-2 isoform were synthesized and secreted by rat MTC 6-23 cell cultures and the tumours induced by subcutaneous injection of these cells. In situ hybridization combined with anti-CT immunocytochemistry showed a low expression of alpha2 mRNA on differentiated C cells and thyrocytes, but an overexpression on immunonegative spontaneous MTC and induced intrathyroid tumours. The high level of alpha2 gene expression, together with tumour dedifferentiation, suggests a relationship with malignancy.

Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases

“…In invasive cancers, laminins usually become discontinuous or absent around tumor foci, which is attributed to either increased degradation or reduced synthesis. At the same time, previously documented changes in the expression of laminin isoforms concerned only α2-chain-containing laminins in basal cell carcinomas, medullary thyroid carcinomas, Schwannomas, and hepatocellular carcinomas [38,40-42]. We have now confirmed these data in breast tumors and their metastases (Table 4).…”

Animal models of medullary thyroid cancer: state of the art and view to the future

“…In zebrafish, starting from 60 h after fertilisation, ultimobranchial bodies are organised in two groups of cells on either side of the heart, in this way, C cells are not in contact with thyroid follicles (Porazzi et al 2009). Thus, zebrafish could help us in understanding if extracellular matrix components, produced by thyroid epithelial, are necessary to the emergence of the MTC phenotype, as previously hypothesised in humans (Lekmine et al 1999).…”

Surgical treatment of differentiated thyroid carcinoma: a retrospective study

“…The identification of a familial form of papillary microcarcinoma (5.9% of carcinomas) has an unfavourable prognostic significance, in spite of the low T score (43). The role of other potential cell markers as useful tools in prognosis or management of DTC have turned out disappointing (laminine, collagenase, K1 antitrypsin) (44,45).…”