Caveolin-1 Is Required for Vascular Endothelial Growth Factor-Triggered Multiple Myeloma Cell Migration and Is Targeted by Bortezomib
Open Access
- 15 October 2004
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 64 (20) , 7500-7506
- https://doi.org/10.1158/0008-5472.can-04-0124
Abstract
We recently demonstrated that caveolae, vesicular flask-shaped invaginations of the plasma membrane, represent novel therapeutic targets in multiple myeloma. In the present study, we demonstrate that vascular endothelial growth factor (VEGF) triggers Src-dependent phosphorylation of caveolin-1, which is required for p130Cas phosphorylation and multiple myeloma cell migration. Conversely, depletion of caveolin-1 by antisense methodology abrogates p130Cas phosphorylation and VEGF-triggered multiple myeloma cell migration. The proteasome inhibitor bortezomib both inhibited VEGF-triggered caveolin-1 phosphorylation and markedly decreased caveolin-1 expression. Consequently, bortezomib inhibited VEGF-induced multiple myeloma cell migration. Bortezomib also decreased VEGF secretion in the bone marrow microenvironment and inhibited VEGF-triggered tyrosine phosphorylation of caveolin-1, migration, and survival in human umbilical vascular endothelial cells. Taken together, these studies demonstrate the requirement of caveolae for VEGF-triggered multiple myeloma cell migration and identify caveolin-1 in multiple myeloma cells and human umbilical vascular endothelial cells as a molecular target of bortezomib.Keywords
This publication has 48 references indexed in Scilit:
- Essential Role of Caveolae in Interleukin-6- and Insulin-like Growth Factor I-triggered Akt-1-mediated Survival of Multiple Myeloma CellsPublished by Elsevier ,2003
- Cholesterol Depletion Disrupts Caveolae and Insulin Receptor Signaling for Metabolic Control via Insulin Receptor Substrate-1, but Not for Mitogen-activated Protein Kinase ControlJournal of Biological Chemistry, 2001
- Antitumor Activity of Thalidomide in Refractory Multiple MyelomaNew England Journal of Medicine, 1999
- p130Cas, an Assembling Molecule of Actin Filaments, Promotes Cell Movement, Cell Migration, and Cell Spreading in FibroblastsBiochemical and Biophysical Research Communications, 1999
- Expression of Caveolin-1 in Human T Cell Leukemia Cell LinesBiochemical and Biophysical Research Communications, 1998
- The Proteasome Is Involved in AngiogenesisBiochemical and Biophysical Research Communications, 1998
- Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cellsNature Medicine, 1996
- De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin.Proceedings of the National Academy of Sciences, 1995
- Caveolin Isoforms Differ in Their N-terminal Protein Sequence and Subcellular Distribution. IDENTIFICATION AND EPITOPE MAPPING OF AN ISOFORM-SPECIFIC MONOCLONAL ANTIBODY PROBEJournal of Biological Chemistry, 1995
- Caveolin, a protein component of caveolae membrane coatsPublished by Elsevier ,1992