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A soluble TGF-beta1 and -beta3 inhibitor lowers collagen type I deposition in experimental anaplastic thyroid carcinoma
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-89581OAI: oai:DiVA.org:uu-89581DiVA: diva2:161184
Available from: 2001-12-17 Created: 2001-12-17 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Tumor Stroma in Anaplastic Thyroid Carcinoma: Interstitial Collagen and Tumor Interstitial Fluid Pressure
Open this publication in new window or tab >>Tumor Stroma in Anaplastic Thyroid Carcinoma: Interstitial Collagen and Tumor Interstitial Fluid Pressure
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy in man with stromal fibrosis as one of the main features. Carcinoma cells synthesized no or little collagen I protein. Pro-α1(I) collagen mRNA was expressed by stromal cells throughout the tumor, but expression of procollagen type I protein was restricted to stromal cells situated close to nests of carcinoma cells. These data suggest that the carcinoma cells stimulated collagen type I deposition by increasing pro-α1(1) collagen mRNA translation.

Cocultures, of the human ATC cell line KAT-4, with fibroblasts under conditions that allow the study of stimulatory factors on collagen mRNA translation, showed that the KAT-4 cells stimulated collagen type I protein synthesis in fibroblasts. Specific inhibitors of PDGF and TGF-β1 and -β3 were able to inhibit this carcinoma cell-induced stimulation of collagen type I synthesis. These findings suggest that tumor cells were able to stimulate collagen mRNA translation in stromal fibroblasts by, at least in part, transferring PDGF and/or TGF-β1 and -β3.

Xenograft transplantation of different ATC cell lines into athymic mice demonstrated that the low collagen producing carcinoma cell lines were less tumorigenic compared to non-collagen producing carcinoma cell lines. The morphology of tumors derived from non-collagen producing ATC cell lines showed a well demarked stroma surrounding carcinoma cell nests.

TGF-β1 and -β3 were found to play a role in generating a high tumor interstitial fluid pressure (TIPF) in experimental KAT-4 tumors. A specific inhibitor of TGF-β1 and -β3 was able to lower TIPF and reduce tumor growth after a prolonged period of treatment, suggesting that TGF-β1 and -β3 have a role in maintaining a stroma that support tumor growth.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2001. 50 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1106
Keyword
Biochemistry, Collagen I synthesis, Fibrosis, Tumor - stroma interactions, PDGF, TGF-β, Inhibitor, Cell cycle, Tumor growth, Hyaluronan, Biokemi
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Medical Biochemistry
Identifiers
urn:nbn:se:uu:diva-1594 (URN)91-554-5198-5 (ISBN)
Public defence
2002-01-07, Lecture hall B21 Uppsala Biomedical Center, Uppsala, 09:15
Opponent
Available from: 2001-12-17 Created: 2001-12-17Bibliographically approved

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