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

Journal of Cellular and Molecular Medicine
Sophie J DeharvengtRadu V Stan

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 i...Continue Reading

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Citations

Nov 13, 2013·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Kenneth M TichauerBrian W Pogue
Oct 16, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Raul ElguetaRadu V Stan
Apr 3, 2019·International Journal of Molecular Sciences·Lucie JaneckovaVladimir Korinek
Sep 8, 2016·Experimental and Therapeutic Medicine·Ling GuoJu Liu
Apr 27, 2019·European Journal of Pharmacology·Yasuhiro NakagamiTatsuya Inoue

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Methods Mentioned

BETA
xenograft
flow cytometry
confocal
fluorescence microscopy
PCR
confocal microscopy
xenografts

Software Mentioned

ImageJ
VassarStats
DIVA
FlowJo
GelEval
Image
CellQuest
Pro Plus

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