Abstract
Abstract Metastatic cancer is marked by the loss of integrity of extracellular matrix (ECM). Adhesion of tumor cells to the ECM mediated by integrins on the surface of the tumor cells is a key step in the initial phase of metastasis. Since ionizing radiation (IR), which is commonly used for cancer therapy can induce alterations of the cell surface, we investigated the effect of IR on the adhesion of breast cancer cells to ECM proteins. Results showed that in MDA-MB-231 breast cancer cell line, IR induced significant increase in both integrin expression and integrin-mediated adhesion to fibronectin, laminin, collagen I and IV. Soluble Arg-Gly-Asp peptide fragments or function-blocking antibodies directed against integrin alpha5beta1 inhibited IR-induced adhesion of MDA-MB-231 cells to fibronectin, indicating that IR-induced adhesion is caused by up-regulation of alpha5beta1 integrin fibronectin receptors. In contrast to MDA-MB-231 cells harboring mutant p53 (R280K), MCF-7 cells (WT p53) were unable to increase adhesion and up-regulation of alpha5beta1 integrin. Interestingly, knockdown of mutant p53 abrogated IR-induced integrin alpha5 integrin expression and adhesion to fibronectin. Our results indicate that mutant p53 coordinates breast cancer cell adhesion through up-regulation of alpha5beta1 integrin. This study suggests that alpha5beta1 integrin might be an effective target to improve the efficacy of radiotherapy in mutant p53 expressing cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4344. doi:1538-7445.AM2012-4344
Published Version
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