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

The mechanisms involved in stromal reactions and fibrosis in solid malignan t 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, ofte n fibrotic malignancy with mesenchymal phenotype, In situ hybridization sho wed the expression of pro-alpha 1(I) collagen mRNA throughout the stromal p art of the tumours, However, immunofluorescence staining using an anti-pro- collagen type I antibody revealed the synthesis of pro-collagen type I prot ein mainly in stromal cells juxtaposed to nests of tumour cells. In one out of five tissue samples from human undifferentiated thyroid carcinomas, pro -alpha 1(I) collagen mRNA expression was also found in a small number of tu mour cells. Several well-characterized cell lines established from undiffer entiated thyroid carcinomas, two from tumours included in the present study , expressed both pro-alpha 1(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 carci noma cells seem to play a regulatory role, stimulating the synthesis of col lagen type I protein in the surrounding stroma by increasing pro-alpha 1(I) collagen mRNA translation. However, collagen type I production by the carc inoma cells might also contribute to the marked desmoplasia commonly seen i n these tumours. Copyright (C) 2000 John Wiley & Sons, Ltd.