Abstract D117: Differential reactivity and cell migration inhibitory functions of autoantibodies to Enolase 1 from African American and European American men with prostate cancer

Abstract

Abstract Prostate cancer (PCa) is the second leading cause of cancer-related deaths in the U.S., with African American (AA) men showing a higher mortality than European American (EA) men. While biological determinants contributing to PCa health disparities remain to be clearly established, there is growing evidence of differences in immunobiology between AA and EA patients with PCa. We demonstrated previously, using immunoproteomic profiling of anti-tumor autoantibody responses in AA and EA patients with PCa, that the glycolytic enzyme enolase 1 (ENO1) is the target of an autoantibody response in subsets of these patients. AA patient sera showed immunoreactivity to ENO1 in a panel of PCa cell lines, as detected by immunoblotting, with lack of reactivity in docetaxel (DTX)-resistant PC3 and DU145 cells. By contrast, anti-ENO1 sera from EA patients and a monoclonal anti-ENO1 antibody (MoAB-ENO1) showed immunoreactivity across the same cell line panel, including DTX-resistant cells. We also noted differences in anti-ENO1 reactivity in ELISA and immunoblots of PCa cell lysates between AA-PCa and EA-PCa patients, suggesting a race-related generation of autoantibodies to different ENO1 variants. ENO1 is a surface protein in cancer cells with roles in plasminogen activation, cell migration, and metastasis. Thus, we explored if anti-ENO1 autoantibodies from AA and EA PCa patients exerted different anti-cancer effects against DTX-sensitive and DTX-resistant PCa cells. Using cell migration assays, we observed that anti-ENO1 sera from EA patients and MoAB-ENO1 reduced the migration of DTX-resistant PC3 and DU145 cells but not that of DTX-sensitive cells. This inhibitory effect was intrinsic to the autoantibodies since purified IgG fraction produced similar results. Further, these inhibitory effects were reversed by pre-absorption of anti-ENO1 sera and purified IgG with recombinant human ENO1. Intriguingly, anti-ENO1 sera from AA patients lacked the same inhibitory effects on the migration of DTX-resistant cells, consistent with their lack of immunoreactivity to ENO1 in these cells. In addition, we observed that MoAB-ENO1, which behaves similar to the anti-ENO1 EA sera, decreased viability without evident cell death, measured by MTT assays and imaging analysis, in both DTX-sensitive and DTX-resistant cells, with a more robust effect on the latter. Together, these results suggest that anti-ENO1 autoantibodies from EA-PCa patients may exert a protective effect by decreasing the migration and proliferation of chemoresistant PCa cells. By contrast, anti-ENO1 autoantibodies from AA PCa patients may lack these protective effects, which could contribute to increased cancer cell migration and metastasis. Further studies are needed to dissect the molecular basis for this race-related differential anti-ENO1 immunoreactivity in PCa patients, and exploit the immunotherapeutic potential of anti-ENO1 antibodies for the treatment of chemoresistant PCa. Citation Format: Carlos Diaz-Osterman, Tino Sanchez, Carlos A Casiano. Differential reactivity and cell migration inhibitory functions of autoantibodies to Enolase 1 from African American and European American men with prostate cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D117.