Abstract 3907: Human pancreatic cancer stem cells utilized to generate an in-vivo mouse/rat model system for screening potential drug candidates for treatment of pancreatic cancer patients

Abstract

Abstract Cancer stem cells (CSCs) are critical for engraftment and long-term growth of many tumors, including pancreatic cancer. The Cancer Stem cells are less sensitive to conventional chemotherapies and radiation therapies, and treatments that can target CSCs are critically needed. Human Pancreatic Cancer is a heterogeneous tumor composed of tumor cells and small fraction of cancer stem cells, with high tumorigenic potential. Pancreatic cancer stem cells are phenotypically similar to the normal stem cells, they express CD133 gene and other genes characteristic of neural stem cells (Nestin) and posses self-renewal potential. The CD133+ Pancreatic CSCs have been isolated with Celprogen Media and ECM and characterized as chemo-/radio-resistant tumor-initiating cells which are responsible as one of the major factors involved in post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ Pancreatic CSCs that resist treatment, we isolated CD133+ Pancreatic CSCs from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ Pancreatic CSCs sorted from the CD133+ Pancreatic CSC spheres express SOX2 ,CD44, Nestin and are capable of clonal self-renewal. We generated in-vivo model systems in mice and rats with these cells to screen potential drug agents for the treatment of Pancreatic Cancer patients. We were capable of generating Pancreatic tumors in mice and rats within 20 days by subcutaneously injecting 1000 Pancreatic CSCs at the hind limbs of the rodents. Within day 5 the Pancreatic CSCs were already present in the rodent's pancreas. At days 10, 15 & 20 the Pancreatic CSCs labeled with GFP were located in the rodent's pancreas. We tested various compound candidates in this model system and we were able to show decrease in Pancreatic tumor when the treatment was started at day 10. We were able to demonstrate gene signatures associated with Pancreatic CSCs in this model system. We do see a down regulation of certain cancer promoter genes in the treatment group when compared to non-treatment groups. Citation Format: Cristian Sharma, Patrick Cleary, Esteban Gomez, Shruthi Satish, Michael Sharma, Michael Perez, Natalee Amecuza, Jitesh Jani, Rubio Punzalan, Jay P. Sharma. Human pancreatic cancer stem cells utilized to generate an in-vivo mouse/rat model system for screening potential drug candidates for treatment of pancreatic cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3907. doi:10.1158/1538-7445.AM2014-3907