Premium
Fibrosis in undifferentiated (anaplastic) thyroid carcinomas: evidence for a dual action of tumour cells in collagen type I synthesis
Author(s) -
Dahlman Thérèse,
Lammerts Ellen,
Wik Majstin,
Bergström Daniel,
Grimelius Lars,
Westermark Kerstin,
Rubin Kristofer,
Heldin NilsErik
Publication year - 2000
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/1096-9896(2000)9999:9999<::aid-path643>3.0.co;2-w
Subject(s) - stromal cell , pathology , type i collagen , biology , cell type , cell culture , cancer research , chemistry , cell , medicine , genetics
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‐α1(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‐α1(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‐α1(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‐α1(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.