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Development and possible clinical use of antagonists for PDGF and TGF-beta
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
2004 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 109, no 3, 165-178 p.Article, review/survey (Other academic) Published
Abstract [en]

Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) are examples of signaling molecules which control the growth, survival motility and differentiation of cells. PDGF stimulates the growth mainly of connective tissue cells, whereas TGF-beta inhibits the growth of most cell types. PDGF and TGF-beta exert their cellular effects by binding to receptors equipped with tyrosine and serine/threonine kinase activities, respectively. Both factors have important roles e.g. during the embryonal development and in wound healing. Overactivity of PDGF or PDGF receptors contributes to the development of certain diseases characterized by excessive cell growth including fibrotic disorders, atherosclerosis and malignancies. Overactivity of TGF-beta also contributes to fibrotic conditions, since TGF-beta promotes accumulation of extracellular matrix molecules. In cancer, TGF-beta is initially a tumor suppressor due to its ability to inhibit cell growth, however, at later stages of tumor progression TGF-beta has tumor promoting activity by enhancing the invasive properties of tumor cells and by suppressing the immune system and promoting angiogenesis. The involvement of PDGF in TGF-beta in serious diseases makes clinically useful antagonists highly desirable. A low molecular weight receptor kinase inhibitor of the PDGF receptor kinase is now tested clinically, and TGF-beta antagonists are under development. The present review discusses the development and possible clinical use of antagonsts for PDGF and TGF-beta.

Place, publisher, year, edition, pages
2004. Vol. 109, no 3, 165-178 p.
Keyword [en]
Animals, Clinical Trials, Drug Design, Humans, Platelet-Derived Growth Factor/*antagonists & inhibitors/metabolism, Transforming Growth Factor beta/*antagonists & inhibitors/metabolism
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-72769PubMedID: 15508523OAI: oai:DiVA.org:uu-72769DiVA: diva2:100680
Available from: 2005-05-30 Created: 2005-05-30 Last updated: 2013-10-31Bibliographically approved

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Heldin, Carl-Henrik
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