Cancer-associated fibroblasts and the role of TGFbeta
2008 (English)In: Transforming Growth Factor-beta in Cancer Therapy, Vol II: Cancer Treatment and Therapy / [ed] Jakowlew, Sonia B., Totowa, NJ: The Humana Press, Inc. , 2008, 417-441 p.Chapter in book (Other academic)
Tumors present a complex composition of cancer and stromal cells that interact by direct cell-to-cell contact, extracellular matrix (ECM) proteins, cytokines, and growth factors. Fibroblasts represent a major cell type in the tumor stroma and participate actively in the process of tumorigenesis. These stromal cells, commonly termed cancer-associated fibroblasts (CAFs), are phenotypically different to their normal counterparts in physiological tissues, and often show myofibroblastic characteristics. Based on similarities with wound healing and inflammatory diseases, transforming growth factor-β (TGF-β) is considered to be the main factor involved in fibroblast recruitment, activation, and also differentiation to myofibroblasts. This review presents experimental evidence on the important role of TGF-β in fibroblast-epithelial interaction, as obtained from in vitro studies and from animal models. Additionally, global gene expression analyses of TGF-β stimulated fibroblasts and CAFs from the in situ environment suggest a TGF-β signature in the tumor stroma. While previous studies support a tumor stimulating effect of TGF-β via fibroblast activation, some recent studies utilizing genetically engineered mice models, indicate an opposite effect on tumor growth. Thus, similar to the dualistic effects of TGF-β on epithelial cells, the TGF-β response on CAFs is also highly context-dependent. The general connection between CAF biology and TGF-β function in tumorigenesis provides a new opportunity for novel stroma-based strategies in anticancer therapy.
Place, publisher, year, edition, pages
Totowa, NJ: The Humana Press, Inc. , 2008. 417-441 p.
cancer-associated fibroblasts, tumor-stroma interaction, myofibroblasts, targeted therapy, TGFB-l ~ microarray, gene expression, cancer
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-144631DOI: 10.1007/978-1-59745-293-9_27ISBN: 978-1-58829-715-0OAI: oai:DiVA.org:uu-144631DiVA: diva2:393960