Abstract B031: Semaphorin 3E promotes pancreatic cancer metastasis through activating stromal cell

Background: Better understanding of the molecular mechanisms of pancreatic adenocarcinoma (PDAC) metastasis is important for the development of effective treatments for this devastating disease. We have previously shown that overexpression of Semaphorin 3E (Sema3E) enhances PDAC cell growth and is associated with poor patient survival. Here, we further determined the effect of Sema3E on stromal cells and the molecular mechanisms contributing to PDAC metastasis. Materials and Methods: Panels of stable PDAC cell lines were generated using either lenti-Sema3E for overexpression or the Crispr/Cas9 system to knock out (KO) Sema3E in both panc28 and panc48 cell lines. The effects of Sema3E overexpression or KO were measured in orthotopically implanted xenograft tumor mouse models in respect to tumor size, metastasis, and survival. After coculture with pancreatic stellate cells (PSCs), the effects of Sema3E on PSC activation were evaluated by GFAP and αSMA staining. Mixtures of PDAC cell lines with PSCs in vivo tumor growth were also evaluated. Result: After orthotopically implanting a panel of Sema3E-overexpressing or knockout panc28 cell lines, we found that the survival span of the sema3E-overexpression cell implant group was significantly shorter than the vector control group (31±9 days vs. 51±15 days) (p Citation Format: Zhengdong Liang, Lin-Kin Yong, George Van Buren, William Fisher, Rosa Hwang, Changyi Chen, Qizhi Cathy Yao. Semaphorin 3E promotes pancreatic cancer metastasis through activating stromal cell [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B031.