PV1 down‐regulation via shRNA inhibits the growth of pancreatic adenocarcinoma xenografts

Journal of Cellular and Molecular Medicine

Sophie J. Deharvengt²  Dan Tse²  Olga Sideleva²  Caitlin McGarry²  Jason R. Gunn³  Daniel S. Longnecker²  Catherine Carriere¹ 

[1] Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA;Departments of Pathology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA;Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

关键词: angiogenesis;    fenestrae;    vesiculo‐vacuolar organelles;    caveolae;    pancreatic cancer;    transendothelial channels;    tumour microenvironment;   

DOI  :  10.1111/j.1582-4934.2012.01587.x

来源: Wiley

【 摘 要 】

Abstract

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two different human pancreatic adenocarcinoma cell lines (AsPC-1 and BxPC-3). The effect observed is because of down-regulation of PV1 in the tumour endothelial cells of host origin, PV1 being specifically expressed in tumour vascular endothelial cells and not in cancer or other stromal cells. There are no differences in vascular density of tumours treated or not with PV1 shRNA, and gain and loss of function of PV1 in endothelial cells does not modify either their proliferation or migration, suggesting that tumour angiogenesis is not impaired. Together, our data argue that down-regulation of PV1 in tumour endothelial cells results in the inhibition of tumour growth via a mechanism different from inhibiting angiogenesis.

【 授权许可】

Unknown   
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd