Abstract 1540: Effect of IGF1 on cancer and stromal cells of human pancreatic tumors
Authors: Kopantseva Marina R. , Usova Eugenia , Mikaelyan Arsen , Kostina Maria , Melekhina Olga , Egorov Vyacheslav , Kopantzev Eugene P. 
Published: August 2015

Background: Insulin-like growth factor 1 (IGF1) exerts a broad anti-apoptotic function, and IGF1/IGF1-receptor (IGF-1R) signaling pathway plays a crucial role in human cancer development and progression. Stromal cells associated with cancer cells are considered an important component of tumor microenvironment, including pancreatic cancers. Previously we have shown an increased expression of IGF1 in pancreatic ductal adenocarcinoma stroma. The goal of our study was to investigate the effect of IGF1 on expression of important for tumor progression genes that regulate epithelial-mesenchymal transition (EMT) in cancer and stromal cells of pancreatic tumors. Methods: The effect of IGF1 was tested on five pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-2, MiaPaCa-2 and Panc1), all cultivated on cell medium with reduced levels of serum. Also, we used primary cultures of pancreatic ductal adenocarcinoma stromal cells on early passages. Gene expression was analyzed via Western Blotting and qRT-PCR. Results: In reduced serum medium IGF1 has been shown to stimulate proliferation in all cell lines and primary cultures. In cancer cell lines MiaPaCa-2 and Panc1 incubation with IGF1 lead to an increase in levels of SNAIL and Zeb1 proteins after 120 hours of incubation. There was an elevation in expression of Twist protein in all cancer cell lines after 120 hours of incubation. However, we have not detected a decrease in levels of epithelial differentiation marker E-cadherin, nor a notable increase in levels of mesenchymal differentiation markers N-cadherin and Vimentin in IGF1-treated cancer cell lines. Only a slight decrease in E-cadherin expression was shown in IGF1-treated AsPC-1 and Panc1 cells. Treatment of primary stromal cells of pancreatic ductal adenocarcinoma with IGF1 results in a slight elevation of N-cadherin and Vimentin expression, as well as a significant increase in anti-apoptotic protein survivin levels. Incubation of stromal cells with specific low-molecular weight inhibitor of IGF-1R was shown to significantly increase levels of SNAI1 gene expression and increase SNAIL protein levels. Conclusions: Analysis of EMT markers and transcription factors in pancreatic cancer cell lines does not allow us to draw conclusions about the ability of IGF1 to cause EMT. Despite increased levels of SNAIL, Zeb1 and Twist proteins, epithelial cancer cells retained stable expression of E-cadherin and did not show an increase in mesenchymal marker expression. In pancreatic tumor stromal cultures IGF1 increases mesenchymal cell phenotype and, evidently, increases cell survival rate by stimulating survivin expression. The effect of IGF-1R inhibitor on the activation of SNAIL expression, as we assume, was caused by interactions between signaling pathways of IGF1 and SHH in stromal cell cultures.

The work is supported by grant of Russian Foundation of Basic Research 13-04-40171-KOMFI

Note: This abstract was not presented at the meeting.

Citation Format: Marina R. Kopantseva, Eugenia Usova, Arsen Mikaelyan, Maria Kostina, Olga Melekhina, Vyacheslav Egorov, Eugene P. Kopantzev. Effect of IGF1 on cancer and stromal cells of human pancreatic tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1540. doi:10.1158/1538-7445.AM2015-1540