Abstract 1526: Alterations in extracellular matrix modulate AR-regulated transcription in prostate cancer cells
Authors: Cynthia Sprenger, Martin Escandon, William Carter, Stephen Plymate
Journal: Cancer Research (2011)

Abstract Introduction: The androgen receptor is a key driver of prostate cancer progression. During progression of prostate cancer alterations to the extracellular matrix occur, including changes in expression of the heterotrimeric glycoprotein laminin (LM), which may alter signaling through the androgen receptor. Purpose: To determine if altered expression of laminin chains affects prostate cancer cell behavior and whether, in androgen receptor (AR) positive lines, AR-regulated transcription is affected by different matrices. Methods: We exposed prostate cancer cell lines (LNCaP, LNCaP C4-2, PC3, and DU145) to different extracellular matrix proteins (fibronectin, collagen I and IV, and laminin 111) as well as to mixed matrices (Matrigel™–LM111 and col IV; and LM-rich prostate cancer derived matrices–LM332, 511 and the LM alpha 4, alpha 4 beta 2, or beta 2 chains). We measured adhesion and proliferation on these different matrices and as well as changes in mRNA expression for AR-regulated genes in the LNCaP lines following exposure to the various matrices. Results: Initially we examined what endogenous laminins the prostate cancer cell lines produced and deposited to determine what they might contribute to the exogenous ECMs tested. When grown on uncoated plastic, we found no expression of LM332 by any of the prostate cancer lines used. Cytoplasmic expression of the LM β1γ1 chains was detected in the lines, but deposition of these laminin chains did not occur. We concluded that these lines are not significantly contributing laminins to the ECM. When exposed to the test ECMs, these prostate cancer lines demonstrated increased adhesion to LM-rich PCa-derived matrices, compared with MatrigelTM, fibronectin, or collagen. An inhibitory integrin beta 1 antibody blocked adhesion to LM-rich PCa-derived matrices by &amp;lt;50%, whereas the same antibody blocked adhesion to fibronectin, collagen, LM111, and Matrigel by &amp;gt;90%, suggesting that additional integrins are involved in adhesion to the LM-rich PCa-derived matrices. When these prostate cancer lines were grown on ECM from LM-rich PCa-derived matrices, increased proliferation resulted compared with proliferation on other ECM components. Exposure of the AR positive LNCaP cells to the different ECM components altered expression of AR-regulated genes, including PSA, TMPRSS2, and IGF-IR. The LM-rich PCa-derived matrices increased expression of these genes compared with exposure to fibronectin, collagen, Matrigel™, and uncoated wells. Summary: Alterations in laminins during progression of prostate cancer affect cancer cell adhesion and proliferation. Further, exposure to LM-rich matrices increased expression of growth promoting AR-regulated genes, which may, in part, modulate cancer cell migration and proliferation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1526. doi:10.1158/1538-7445.AM2011-1526