Cancer Cell International 2006-01-01

Prostate cancer cells show elevated urokinase receptor in a mouse model of metastasis.

Inder Sehgal, Timothy P Foster, Joseph Francis

Index: Cancer Cell Int. 6 , 21, (2006)

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Abstract

The urokinase receptor (uPAR) governs several functions necessary during invasion and metastasis such as motility, degradation of the extracellular matrix and adhesion. This receptor has been recently associated with clinical prostate cancer progression. Experimentally, inhibition of uPAR reduces colonization of extra-prostatic sites in animal models. Our objective in this study was to compare uPAR expression in orthotopic vs. metastatic foci in vivo and to examine at the cellular level how uPAR might promote early stages of metastasis.We show that uPAR staining is significantly greater in regional lymph node metastases than in the intraprostatic tumor mass. Using transient over-expression, we found that uPAR increases in vitro motility and chemotactic invasion. Finally, we demonstrate that uPAR is up-regulated by a significant subpopulation prostate cancer cells following matrix detachment and maintenance in suspension and we provide evidence that prostate cancer cells with elevations in uPAR have an enhanced resistance to anoikis.These data provide new evidence that uPAR can be induced by cancer cells during metastasis in vivo and that this elevated uPAR enhances resistance to anoikis in vitro.