This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goel, H. L. Articles by Languino, L. R. Search for Related Content PubMed PubMed Citation Articles by Goel, H. L. Articles by Languino, L. R.

ß₁ Integrins Modulate Cell Adhesion by Regulating Insulin-Like Growth Factor-II Levels in the Microenvironment

¹ Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts; Departments of ² Pathology and ³ Surgery, Yale University School of Medicine, New Haven, Connecticut; ⁴ Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania; and ⁵ Institute of Biomembranes and Bioenergetics, National Council of Research, Bari, Italy

Requests for reprints: Lucia R. Languino, Department of Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605. Phone: 508-856-1606; Fax: 508-856-3845; E-mail: lucia.languino{at}umassmed.edu.

The interactions between cancer cells and the extracellular matrix (ECM) regulate cancer progression. The ß_1C and ß_1A integrins, two cytoplasmic variants of the ß₁ integrin subfamily, are differentially expressed in prostate cancer. Using gene expression analysis, we show here that the ß_1C variant, an inhibitor of cell proliferation, which is down-regulated in prostate cancer, up-regulates insulin-like growth factor-II (IGF-II) mRNA and protein levels. In contrast, ß_1A does not affect IGF-II levels. We provide evidence that ß_1C-mediated up-regulation of IGF-II levels increases adhesion to Laminin-1, a basement membrane protein down-regulated in prostate cancer, and that the ß_1C cytoplasmic domain contains the structural motif sufficient to increase cell adhesion to Laminin-1. This autocrine mechanism that locally supports cell adhesion to Laminin-1 via IGF-II is selectively regulated by the ß₁ cytoplasmic domain via activation of the growth factor receptor binding protein 2–associated binder-1/SH2-containing protein-tyrosine phosphatase 2/phosphatidylinositol 3-kinase pathway. Thus, the concurrent local loss of ß_1C integrin, of its ligand Laminin-1, and of IGF-II in the tumor microenvironment may promote prostate cancer cell invasion and metastasis by reducing cancer cell adhesive properties. It is, therefore, conceivable that reexpression of ß_1C will be sufficient to revert a neoplastic phenotype to a nonproliferative and highly adherent normal phenotype. (Cancer Res 2006; 66(1): 331-42)

This article has been cited by other articles:

				H. L. Goel, L. Moro, J. E. Murphy-Ullrich, C.-C. Hsieh, C.-L. Wu, Z. Jiang, and L. R. Languino {beta}1 Integrin Cytoplasmic Variants Differentially Regulate Expression of the Antiangiogenic Extracellular Matrix Protein Thrombospondin 1 Cancer Res., July 1, 2009; 69(13): 5374 - 5382. [Abstract] [Full Text] [PDF]

				H.-V. Wang, L.-W. Chang, K. Brixius, S. A. Wickstrom, E. Montanez, I. Thievessen, M. Schwander, U. Muller, W. Bloch, U. Mayer, et al. Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage J. Cell Biol., March 5, 2008; 180(5): 1037 - 1049. [Abstract] [Full Text] [PDF]

				C.-Q. Zhu, S. N. Popova, E. R. S. Brown, D. Barsyte-Lovejoy, R. Navab, W. Shih, M. Li, M. Lu, I. Jurisica, L. Z. Penn, et al. Integrin {alpha}11 regulates IGF2 expression in fibroblasts to enhance tumorigenicity of human non-small-cell lung cancer cells PNAS, July 10, 2007; 104(28): 11754 - 11759. [Abstract] [Full Text] [PDF]

				L. Moro, A. A. Arbini, E. Marra, and M. Greco Up-regulation of Skp2 after Prostate Cancer Cell Adhesion to Basement Membranes Results in BRCA2 Degradation and Cell Proliferation J. Biol. Chem., August 4, 2006; 281(31): 22100 - 22107. [Abstract] [Full Text] [PDF]