Fibrosis in undifferentiated (anaplastic) thyroid carcinomas: evidence for a dual action of tumour cells in collagen type I synthesis.

The mechanisms involved in stromal reactions and fibrosis in solid malignant tumours are incompletely understood. In the present study, collagen type I production was investigated in tissues and cell lines derived from human undifferentiated (anaplastic) thyroid carcinomas, a highly aggressive, often fibrotic malignancy with mesenchymal phenotype. In situ hybridization showed the expression of pro-alpha1(I) collagen mRNA throughout the stromal part of the tumours. However, immunofluorescence staining using an anti-pro-collagen type I antibody revealed the synthesis of pro-collagen type I protein mainly in stromal cells juxtaposed to nests of tumour cells. In one out of five tissue samples from human undifferentiated thyroid carcinomas, pro-alpha1(I) collagen mRNA expression was also found in a small number of tumour cells. Several well-characterized cell lines established from undifferentiated thyroid carcinomas, two from tumours included in the present study, expressed both pro-alpha1(I) collagen and prolyl 4-hydroxylase mRNA, and three of these cell lines also synthesized native triple-helical collagen type I. Taken together, these data suggest that stromal fibroblasts are the main producers of collagen type I in anaplastic thyroid tumours. The carcinoma cells seem to play a regulatory role, stimulating the synthesis of collagen type I protein in the surrounding stroma by increasing pro-alpha1(I) collagen mRNA translation. However, collagen type I production by the carcinoma cells might also contribute to the marked desmoplasia commonly seen in these tumours. Copyright 2000 John Wiley & Sons, Ltd.