Abstract 2343: Overexpression of uPAR in the murine oral squamous cell carcinoma cell line AT84

Abstract

Abstract Cancers of the oral cavity are associated with bad prognosis and have been so for the last 20-30 years. Almost half of the patients diagnosed with oral squamous cell carcinoma (SCC) will die from the disease. When comparing oral SCC to its counterpart in skin, one of the main features that differ between the two is the ability of the oral SCC to metastasize. A prerequisite for metastasis is the capability to invade the surrounding tissue and penetrate into the nearest blood- or lymphatic vessel. This initial step in metastasis requires several extracellular matrix degrading enzymes. One such enzyme is uPA (urokinase-type plasminogen activator), involved in pericellular proteolysis, where high levels are known to be correlated to bad prognosis in several cancers. Pro-uPA binds to its extracellularly located receptor uPAR. Upon binding, pro-uPA is cleaved and activated, and ample evidence shows that binding of uPA triggers uPAR-mediated cellular signalling. Being that uPAR has no membrane spanning domain, the signal transduction has to be mediated through one or several membrane partners. uPARs role in the regulation of cell adhesion, migration and proliferation have been dedicated to its interplay with membrane partners such as integrins, chemokine receptors, EGFR, G-protein coupled receptors and caveolin. To better understand the role of uPAR in the metastasis of oral SCCs, a mouse oral SCC cell line, AT84, was stably transfected with uPAR. AT84 was initially obtained from a spontaneously originating oral SCC of the C3H mouse (Lou et al., 2003; Schultz-Hector and Haghayegh, 1993). Characterization of these cell lines with respect to adhesion, migration, invasion, and effects on gene expression and activation of other proteolytic enzymes will be presented. Lou, E., R.M. Kellman, R. Hutchison, and E.J. Shillitoe. 2003. Clinical and pathological features of the murine AT-84 orthotopic model of oral cancer. Oral Dis. 9:305-12. Schultz-Hector, S., and S. Haghayegh. 1993. Beta-fibroblast growth factor expression in human and murine squamous cell carcinomas and its relationship to regional endothelial cell proliferation. Cancer Res. 53:1444-9. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2343.