Expression of Kallikrein 7 Diminishes Pancreatic Cancer Cell Adhesion to Vitronectin and Enhances Urokinase-Type Plasminogen Activator Receptor Shedding


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Abstract

Objectives:To examine the effects of kallikrein 7 (KLK7) expression in pancreatic cancer cells on cell adhesion to extracellular matrix proteins.Methods:Kallikrein 7 was overexpressed in the pancreatic cancer cell line BxPC-3, and in vitro cell adhesion assays were performed to determine alterations in cell adhesion to collagen I, fibronectin, and vitronectin compared with vector-transfected cells. Changes in cell surface expression of αvβ3 integrin were examined by flow cytometry, and the release of soluble urokinase-type plasminogen activator receptor (uPAR) was monitored by Western blot analysis.Results:The expression of KLK7 in BxPC-3 cells led to reduced adhesion to vitronectin but not collagen I or fibronectin. Loss of cell adhesion to vitronectin was not caused by changes in the level of αvβ3 integrin cell surface expression; however, a significant increase in the amount of uPAR shed was observed in KLK7-expressing cells compared with vector-transfected control cells.Conclusions:The aberrant expression of KLK7 in pancreatic cancer cells leads to a reduction in cell adhesion to vitronectin that may result from the cleavage of uPAR from the cell surface. Kallikrein 7 expression, therefore, may play an important role in the dissemination of tumor cells through the production of soluble uPAR in pancreatic cancer and perhaps other human malignancies.

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