uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
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.
Show others and affiliations
Manuscript (Other academic)
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.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1106
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
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
Available from: 2001-12-17 Created: 2001-12-17Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Medical Biochemistry and Microbiology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 152 hits
ReferencesLink to record
Permanent link

Direct link