Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 13, Issue 9B, Pages 3449-3462Publisher
WILEY
DOI: 10.1111/j.1582-4934.2008.00638.x
Keywords
myofibroblast; pericyte; integrin connective tissue; adenocarcinoma rheumatoid arthritis; matrigel
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Funding
- Swedish Cancer Foundation
- Swedish Research Council
- Children's Cancer Foundation
- Gustav V 80 Year Foundation
- Georg Wally Foundation
- Clas Groschinsky Foundation
- Swedish Society of Physicians
- UAS Cancer Foundation
- Mary Ake and Hans Landells Foundation
- Ake Wiberg Foundation
- Lions Cancer Foundation
- Agnes and Mac Rudbergs Foundation
- Hans Jeanssons Foundation
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Connective tissue cell activation is of importance during reactive conditions such as solid tumour growth, wound healing and pannus formation in rheumatoid arthritis. Here, we have compared connective tissue cells of mesenchymal origin in human tissues from these conditions and their normal counterparts using a panel of cell-type-specific markers. In particular, we investigated variations of integrin expression among connective tissue cell phenotypes. Connective tissue cell populations were defined based on their association with the microvasculature and their expression of activation markers. The phenotype of these cells varied according to the type of pathological connective tissue examined. Our morphological data from human tissues suggested that the alpha(1)beta(1) integrin, a collagen/laminin receptor, is involved in the differentiation of precursor cells into myofibroblasts. To mechanistically investigate this hypothesis, we employed experimental models for carcinoma growth and wound healing utilizing alpha(1) integrin-deficient mice. The data confirmed that the alpha(1)beta(1) integrin is of importance not only for the differentiation of mesenchymal cells into myofibroblasts but also for the neovascularization and connective tissue organization and emphasize the importance of myofibroblasts in the pathophysiology of tissue repair, inflammation and tumour growth.
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