Antiproliferative effects of polyclonal antibody against (pro) renin receptor in pancreatic ductal adenocarcinoma cells

[Speaker] Asadur Rahman:1,2
[Co-author] Yuki Shibayama:2, Arif Ul Hasan:1,2, Hirofumi Hitomi:2, Daisuke Nakano:2, Hiroyuki Kobori:1, Akira Nishiyama:2
1:Department of Pharmacology, International University of Health and Welfare, Japan, 2:Department of Pharmacology, Faculty of Medicine, Kagawa University, Japan

Background: Despite a remarkable progress in the treatment strategy for pancreatic ductal adenocarcinoma (PDAC, the prognosis remains strikingly poor. Recently, we have reported that silencing of (pro)renin receptor ((P)RR) significantly blunted the Wnt/β-catenin-dependent tumorigenesis of PDAC.
Methods: To extend our previous study, we developed seven (P)RR antisera and subsequently, a neutralizing polyclonal antibody (pAb) against the epitopes targeting the extracellular domain of the (P)RR, and investigated the anti-proliferative effects in PDAC cells, namely PK-1 and PANC-1.
Results: We observed that antiserum 3 (against an epitope that comprising amino acids 200-213) significantly reduced the PDAC cell proliferation in vitro as well as xenograft tumor volume in athymic nude mice in vivo. Consistently, pAb against the same epitope also attenuated the PDAC cell proliferation in a dose-dependent manner and downregulated the expression of active β-catenin expression in vitro. Furthermore, systemic administration of (P)RR pAb significantly reduced the tumor volume in a subcutaneous PK-1 xenograft model. Immunohistochemistry of xenograft tissue from the mice treated with pAb revealed a substantial reduction of ki-67 and active β-catenin immunoreactivity.
Conclusions: These results suggest that (P)RR pAb has the potential to suppress cell proliferation by hindering the activation of Wnt/β-catenin signaling in PDAC cells. Therefore, neutralizing the (P)RR by means of antibody could be an attractive therapeutic approach for PDAC.

Advanced Search