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.
Department of Medical Biochemistry and Microbiology, Biomedical Center, SE-751 23 Uppsala, Sweden.
T
T
Dahlman
E
E
Lammerts
M
M
Wik
D
D
Bergström
L
L
Grimelius
K
K
Westermark
K
K
Rubin
N E
NE
Heldin
D015152:Blotting, Northern; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000096:biosynthesis*; D017364:Collagenases / Q000378:metabolism; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D006801:Humans; D017403:In Situ Hybridization; D012333:RNA, Messenger; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D003094:Collagen; D017364:Collagenases