Abstract 3402: Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer

Abstract Purpose: We previously reported that activin produces a signal with a tumor suppressive role in pancreatic cancer (PC). Here, the association between plasma activin A and survival in patients with advanced PC was investigated. Experimental Design: The plasma activin A concentrations of patients with advanced PC were determined using an ELISA. The influence of ligands on PC cell lines was evaluated using an MTT assay and western blot analyses. The INHBA gene (beta subunit of inhibin) was overexpressed in PC cell lines, and this phenotype was investigated. Results: Contrary to our expectations, patients with high plasma activin A levels had a significantly shorter survival period than those with low levels (median survival, 314 days vs. 482 days, P = 0.034). The cellular growth of the MIA PaCa-2 cell line was greatly enhanced by activin A via non-SMAD pathways. The cellular growth and colony formation of an INHBA-overexpressed cell line were also enhanced. In a xenograft study, INHBA-overexpressed cells tended to result in a larger tumor volume, compared with a control. The bodyweights of mice inoculated with INHBA-overexpressed cells decreased dramatically, and these mice all died at an early stage, suggesting the occurrence of activin-induced cachexia. Conclusions: Our findings indicated that the activin signal can promote cancer progression in a subset of PC and might be involved in cachexia and that plasma activin A can be a novel prognostic factor in patients with advanced PC. The activin signal might be a novel target for the treatment of PC. Citation Format: Yosuke Togashi, Akihiro Kogita, Hiroki Sakamoto, Hidetoshi Hayashi, Masato Terashima, Marco A. de Velasco, Kazuko Sakai, Yoshihiko Fujita, Shuta Tomida, Masayuki Kitano, Masatoshi Kudo, Kazuto Nishio. Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer. [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 3402. doi:10.1158/1538-7445.AM2015-3402