?3 integrins facilitate matrix interactions during transendothelial migration of PC3 prostate tumor cells

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Abstract
BACKGROUND β3 integrins play a role in metastatic progression of prostate cancer by mediating adhesion of cancer cells to endothelium and migration through extracellular matrix (ECM). However, the role of β3 integrins during transendothelial migration (TEM) of prostate tumor cells is poorly understood. We examined the role of β3 integrins in TEM of PC3 human prostate cancer cells through a monolayer of human lung microvascular endothelial cells (HLMVECs). METHODS PC3 cells were challenged with β3 integrin antibodies or antisense nucleotides and their efficiency to migrate through monolayers of endothelial cells (ECs) was assessed using confocal microscopy. RESULTS β3 integrins in PC3 cells are not localized in focal contacts and their blockade significantly inhibited TEM by over 50% preferentially during late stages of migration. Formation of PC3 cell pseudopodia on matrigel was significantly reduced by β3 integrin antisense oligonucleotides. CONCLUSIONS β3 integrins play important roles during TEM of PC3 cells while interacting with the matrix underneath the endothelium. These interactions are independent of the ability to cluster β3 integrins into focal adhesions.