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p11 Regulates extracellular plasmin production and invasiveness of HT1080 fibrosarcoma cells

Cancer Biology Research Group,
^* Department of Medical Science,
^¶ Department of Biochemistry and Molecular Biology and Oncology, University of Calgary Calgary, Alberta, Canada T2N4N1

¹Correspondence: Departments of Biochemistry and Molecular Biology and Oncology, Faculty of Medicine, University of Calgary, 3330 Hospital Dr., N.W., Calgary, Alberta T2N 4N1, Canada. E-mail: waisman{at}ucalgary.ca

The defining characteristic of a tumor cell is its ability to escape the constraints imposed by neighboring cells, invade the surrounding tissue, and metastasize to distant sites. This invasive property of tumor cells is dependent on activation of proteases at the cell surface. Most cancer cells secrete the urokinase-type plasminogen activator, which converts cell-bound plasminogen to plasmin. Here we address the issue of whether the plasminogen binding protein, p11, plays a significant role in this process. Transfection of human HT1080 fibrosarcoma cells with the human p11 gene in the antisense orientation resulted in a loss of p11 protein from the cell surface and concomitant decreases in cellular plasmin production, ECM degradation, and cellular invasiveness. The transfected cells demonstrated reduced development of lung metastatic foci in SCID mice. In contrast, HT1080 cells transfected with the p11 gene in the sense orientation displayed increased cell surface p11 protein and concomitant increases in cellular plasmin production, as well as enhanced ECM degradation and enhanced cellular invasiveness. The p11 overexpressing cells showed enhanced development of lung metastatic foci. These data establish that changes in the extracellular expression of the plasminogen receptor protein, p11, dramatically affect tumor cell-mediated pericellular proteolysis.—Choi, K.-S., Fogg, D. K., Yoon, C. S., Waisman, D. M. p11 regulates extracellular plasmin production and invasiveness of HT1080 fibrosarcoma cells.

Key Words: annexin • S100A10 • p11 • plasminogen • plasmin • urokinase • cancer

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