Abstract B97: Exosomal survivin, a potential tool for early detection of pancreatic cancer health disparity?

Introduction: Pancreatic cancer is a fatal disease that needs immediate attention to develop better screening or early diagnostic tools. African American populations have 42% higher pancreatic cancer death rates than Caucasians. These differences may modify various phases of the multistage process of carcinogenesis by molecular, genetic, and biologic aspects of cancer health disparities. Survivin is expressed in many cancers and its downregulation sensitizes cancer cells to chemotherapeutic agents in vitro and in vivo. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion, and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose early or monitor pancreatic cancer prognosis in African American populations. Methods: Caucasian-derived Panc1 (control) and African American-derived (KCI-Moh) cell lines were treated with sublethal dosages of cobalt chloride (CoCl2) and gemcitabine. Conditioned media and cell lysates were collected. Exosomes were purified from both cell lines using ultracentrifugation and their quantities and qualities were quantified and visualized from the purified exosomes using ELISA and Western blotting, respectively. Results: Survivin was significantly higher in the exosomes purified from the KCI-Moh cell line's conditioned media compared to those from Panc1 (with and without treatment) although higher quantities of exosomes were noted with the different treatments in Panc1. Exosomal survivin levels were higher in KCI-Moh with CoCl2 as well as gemcitabine compared to controls. Conclusions: These studies demonstrate that survivin exists in exosomes from both Panc1 and KCI-Moh cell lines, and higher concentrations of survivin were observed in KCI-Moh-derived conditioned media. However, increased exosomal survivin levels were observed after Gemcitabine treatment. The relative exosome quantity was significantly higher when treated with CoCl2 and Gemcitabine in Panc1. This differential expression of survivin in the media and exosomes from KCI-Moh may be responsible for chemoresistance or aggressiveness in African American-derived cell lines. Further analysis of plasma exosomal survivin levels may offer a convenient tool for diagnosing or monitoring pancreatic cancers and may be used for early detection in African American populations. Citation Format: Salma Khan, Jessica M.S. Jutzy, Jonathan R. Aspe, Nathan R. Wall. Exosomal survivin, a potential tool for early detection of pancreatic cancer health disparity? [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B97.