Abstract
Abstract A. BACKGROUND/AIMS Pancreatic cancer is one of the most lethal diseases, which is difficult to diagnose and resistant to conventional treatment such as chemotherapy and radiotherapy. Cancer stem cells are involved in carcinogenesis, cancer progression and recurrence. We tried to find secretory biomarkers associated with pancreatic cancer stem cells using proteomic analysis. B. METHODS Pancreatic cancer stem like cells were enriched using sphere culture method. Proteomic analysis was done with secreted protein in culture medium of sphere and adherent cells. Identified proteins were confirmed with Western blot and immunohistochemical staining. ELISA was done to detect blood levels of validated proteins in pancreatic cancer patients. shRNA for GLRX3 was used to study the function of GLRX3 in pancreatic cancer. C. RESULTS Proteomic analysis showed that total of 55 protein spots from sphere cells were increased compared to adherent cells. Among them, 41 spots were identified using MALDI-TOF. Proteins known to be associated with cancer stem cells such as HSP90AB1, ALDH, and vimentin were expressed in sphere cells. The overexpression of 5 proteins including GLRX3 was confirmed by western blot in sphere cells and patient serum. Immunohistochemical staining in TMA of human pancreatic cancer tissue revealed that GLRX3 was detected in 15 (57.7%) out of 25 pancreatic cancer tissues regardless of cancer stages. To examine GLRX3 involvement in pancreatic carcinogenesis, we used shRNA to generate GLRX3-knockdown cells. Compared to the mock, knockdown of GLRX3 in human pancreatic cancer cell lines decreased in vitro proliferation, clonogenecity, and sphere formation. GLRX3 knockdown reverses epithelial-mesenchymal transition in pancreatic cancer cells. ELISA showed patients with unresectable pancreatic cancer and high blood GLRX3 levels had poor survival compared to those with low blood GLRX3 levels (155 days vs 463 days, p-value <0.000). D. CONCLUSION This study shows that secretory protein GLRX3 may be a useful prognostic marker in pancreatic cancer. More researches are needed to find their roles in cancer stem cells and clinical implication. 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 713. doi:1538-7445.AM2012-713
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