Abstract 4959: Targeting pancreatic stellate cells (PSC) to treat pancreatic cancer.

Abstract

Abstract Pancreatic cancer (PC) is characterized by a prominent stromal reaction. Recently, the contribution of the stromal elements to the initiation and progression of the disease has come to be appreciated. In this context, targeting this tumor microenvironment represents a potential strategy to improve the delivery and efficacy of chemotherapeutic agents leading a better prognosis for the patients. Pancreatic stellate cells (PSC) have been recognized as the principal cells responsible for the production of fibrosis in pancreatic cancer. In the current study, we observed that PSC possess α-naphthyl acetate esterase (ANAE) activity, which is a specific marker enzyme for monocytes and macrophages, these cells can be differentiated/activated in a similar fashion as a monocytes/macrophages, suggesting that PSC behave in a similar fashion as macrophages, and hence can be treated as such. Based on these data we targeted PSC in vitro and in vivo by using bisphosphonates (BPs) that are macrophages inhibitors. BPs inhibited proliferation and inactivated PSC in vitro through inhibition of protein prenylation, and increased cell apoptosis and cell cycle arrest in G1. Furthermore, BPs inactivated PSC, inhibited tumor growth (p<0.0005), tumor weight (p<0.001) and number of nodules (p<0.001) in an orthotopic animal model of pancreas. These antitumor effects were enhanced when BPs were combined with a taxane. These data suggest that BPs could disrupt the pancreatic cancer, which could offer a better prognosis to PC patients. Citation Format: Vianey Gonzalez-Villasana, Cristian Rodriguez-Aguayo, Thiru Arumugam, Zobeida Cruz-Monserrate, Defeng Deng, Enrique Fuentes-Mattei, Rosa F. Hwang, Huamin Wang, Guillermo N. Armaiz Pena, Burcu Aslan, Yolanda Gutierrez-Puente, Anil K. Sood, Craig Logsdon, Gabriel Lopez-Berestein. Targeting pancreatic stellate cells (PSC) to treat pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4959. doi:10.1158/1538-7445.AM2013-4959