The Effect of Aquaporin 1-Inhibition on Vasculogenic Mimicry in Malignant Mesothelioma

International Journal of Molecular Sciences
Emily PulfordSonja Klebe

Abstract

Malignant mesothelioma (MM) is an aggressive malignancy of the serosal membranes, with poor overall survival and quality of life. Limited targeted treatment strategies exist due to restricted knowledge of pathogenic pathways. Vasculogenic mimicry (VM) is a newly described phenomenon associated with increased aggressiveness in other malignancies, and has been characterized in MM. Normal mesothelium expresses aquaporin 1 (AQP1) and retained expression has been associated with improved survival in MM. AQP1 is expressed by normal vascular endothelium and is involved in mediating MM cell motility and proliferation. We investigated the role of AQP1 in VM, and its interaction with the pro-angiogenic factor vascular endothelial growth factor A (VEGFA), which is variably expressed in MM. Matrigel VM assays were performed using NCI-H226 and NCI-H28 MM cell lines and primary cells in hypoxia and normoxia. The synthetic blocker AqB050 and siRNA were used to inhibit AQP1, and bevacizumab was used to inhibit VEGF. Inhibition of AQP1 resulted in increased VEGFA secretion by MM cells and reduced VM in MM cell lines in hypoxia but not normoxia. No change in VM was seen in MM primary cells. Combined inhibition of AQP1 and VEGF had no effect on V...Continue Reading

References

Jan 1, 1994·Cytogenetics and Cell Genetics·P M DeenC H van Os
Jan 20, 1995·The Journal of Biological Chemistry·G L Wang, G L Semenza
Jul 26, 1996·The Journal of Biological Chemistry·B H JiangG L Semenza
Jun 1, 1997·The Journal of Pathology·S Kumar-SinghE Van Marck
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·L E HuangH F Bunn
Sep 17, 1999·The American Journal of Pathology·A J ManiotisM J Hendrix
Nov 18, 2000·American Journal of Physiology. Cell Physiology·Y SongA S Verkman
Feb 21, 2003·International Journal of Cancer. Journal International Du Cancer·Rizwan MasoodParkash S Gill
Sep 20, 2005·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·A KlabatsaD A Fennell
Aug 4, 2007·The Journal of Biological Chemistry·Miriam EchevarríaJosé López-Barneo
Jul 1, 2009·International Journal of Experimental Pathology·Carolyn A StatonNicola J Brown
Nov 3, 2010·Respiratory Medicine·Noriko HirayamaTakashi Nakano
Oct 4, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Linda L GarlandDavid R Gandara
Jun 6, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hedy L KindlerEverett E Vokes
Jul 10, 2012·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jonathan E DowellHedy Lee Kindler
Aug 17, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Anna K NowakMichael J Byrne
Sep 3, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Zhifei CaoQuansheng Zhou
Sep 17, 2014·Journal of Visualized Experiments : JoVE·Katie L DeCicco-SkinnerJonathan S Wiest
Jul 5, 2016·International Journal of Molecular Sciences·Jack DrimlSonja Klebe

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