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Biochem Biophys Res Commun. 2000 Mar 24;269(3):652-9.

Rho-kinase inhibitor retards migration and in vivo dissemination of human prostate cancer cells.

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  • 1Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, Virginia 22906, USA. avs5u@virginia.edu

Abstract

The Rho-kinase inhibitor, Y-27632, inhibited in vitro chemotactic migration to bone marrow fibroblast conditioned media and metastatic growth in immune-compromised mice of highly invasive human prostatic cancer (PC3) cells. Y-27632 also reduced myosin light chain phosphorylation and markedly altered the morphology of cells that developed numerous processes containing microtubules. A strikingly different, rounded phenotype was induced by an inhibitor of myosin light chain kinase, ML9. The M(110-130) subunit of the myosin phosphatase that is regulated by Rho-kinase was present in PC3 cells that contained significantly more RhoA than the less invasive, LNCaP cells. Y-27632 also inhibited angiogenesis as measured by endothelial cell tube formation on Matrigel. We conclude that invasiveness of human prostate cancer is facilitated by the Rho/Rho-kinase pathway, and exploration of selective Rho-kinase inhibitors for limiting invasive progress of prostate cancer is warranted.

Copyright 2000 Academic Press.

PMID:
10720471
[PubMed - indexed for MEDLINE]
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