Integrin Expression

With the exception of red blood cells, all major cell types express integrins.1,2 Some integrins are cell type specific, e.g. aIIbp3 integrin for platelets, but most integrins are expressed in a variety of tissues. The cellular integrin pattern is not stable, but regulated at different stages of differention as well as at the stimulation of growth factor and cytokine action. Peptide factors known to modify integrin gene expression include transforming growth factors-p (TGF-p),27,28 interferon-y (IFN-y),29 epidermal growth factor (EGF),30 bone morphogenetic protein-2 (BMP-2),31 platelet derived growth factor (PDGF),32 interleukin-1 (IL-1),33 and tumor necrosis factor a (TNF-a).29,33

While the expression of some integrins has been linked to malignant cell phenotype, most are considered markers of more differentiated cells.4,5 Integrin a2p1 has been described as the melanoma progression antigen34 and it is upregulated by malignant transformation of osteogenic cells.35 In vitro studies, a2p1 enhances the invasion of cells through type I collagen gels and basement membranes.36,37 Overexpression of a5p1 integrin on hamster ovary cells reduces their tumorigenity.38 While in highly invasive colon carcinoma cells the integrin is expressed in elevated levels compared to less malignant ones, suggesting that in these cells a5p1 integrin contributes to malignant progression.39 Integrin aVp3 is needed for angiogenesis and is often upregulated in cells with invasive and metastatic capacity.40 Antagonists for aVp3 integrin successfully disrupted human tumors transplanted onto chick chorioallantoid membrane.41 Using differential display to evaluate mRNA, it has been shown that a6 can function as a putative tumor suppressor gene in breast cancer cells.42

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