Altered Integrin Expression and the Malignant Phenotype: The Contribution of Multiple Integrated Integrin Receptors
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- Zutter, M.M., Sun, H. & Santoro, S.A. J Mammary Gland Biol Neoplasia (1998) 3: 191. doi:10.1023/A:1018798907544
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The integrins are a family of cell surfaceadhesion receptors that mediate adhesion to eithercomponents of the extracellular matrix or to othercells. The β1 family of integrinsrepresent the major class of cell substrate receptors withspecificities primarily for collagens, laminins, andfibronectins. The role of the integrin family of cellsurface adhesion receptors in normal mammary glandmorphogenesis and the contributions of altered integrinreceptor expression to the invasive and metastaticphenotype have been the primary focus of our lab, aswell as a number of other laboratories. Theα2 β1 integrin is expressed at high levels by normaldifferentiated epithelial cells including those of thenormal breast. Using breast cancer as a model, weevaluated changes in integrin expression in malignancy. We and other investigators made the keyobservation that α2 β1integrin expression is decreased in adenocarcinoma ofthe breast in a manner that correlates with the stage ofdifferentiation. Studies of other adenocarcinomas have yielded similarresults. When the α2 β1integrin was reexpressed in a poorly differentiatedmammary carcinoma that expressed no detectableα2 integrin subunit, a dramatic reversion of malignant phenotype to adifferentiated epithelial phenotype was observed,indicating a critical role forα2β1 expression inmammary gland differentiation. Other laboratories using monoclonal antibodies to competitivelyinhibit α2 β1 integrinadhesion or oncogenic transformation using c-erb2 haveconfirmed the important role of that α2β1 integrin in mammary gland morphogenesis. Re-expression of theα2 β1 integrin alsoresults in upregulation of both the α6and β4 integrin subunits. To determinethe contribution of enhanced α6 andβ4 integrin expression to the abrogation of the malignantphenotype by α2 β1integrin expression, we have now separately re-expressedthe human α6 or β4integrin subunit in the breast cancer model.