Vesicle-associated urokinase plasminogen activator promotes invasion in prostate cancer cell lines
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The ability of a cell to modify the extracellular matrix is important in several pathophysiological alterations including tumorigenesis. Cell transformation is accompanied by changes in the surrounding stroma as a result of the action of specific proteases such as the urokinase plasminogen activator (uPA), which has been associated with invasive potential in many tumor types. In this study, we analyzed the release of vesicle-associated uPA by the aggressive prostatic carcinoma cell line PC3 and the implications of this release for the invasive behaviour of prostatic tumor cells. Zymography and Western blot analysis revealed the presence of vesicle-associated uPA in the high-molecular weight form. Vesicles adhered to and degraded both collagen IV and reconstituted basal membrane (Matrigel), and plasminogen enhanced the degradation in a dose-dependent manner. Addition of membrane vesicles shed by PC3 cells to cultures of the poorly invasive prostate cancer cell line LnCaP enhanced the adhesive and invasive capabilities of the latter, suggesting a mechanism involving substrate recognition and degradation. Together, these findings indicate that membrane vesicles can promote tumor invasion and point to the important role of vesicle-associated uPA in the extracellular compartment.
- Reich E. Activation of plasminogen: a general mechanism for producing localized extracellular proteolysis. In Berlin RD, Hermann H, Lepow IH, Tanzer JM (eds): Molecular Basis of Biological Degradative Processes. New York: Academic Press 1978; 155–69.
- Mignatti P, Rifkin DB. Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 1993; 7: 161–95.
- Basbaum CB, Werb Z. Focalized proteolysis: spatial and temporal regulation of extracellular matrix degradation at the cell surface. Curr Opin Cell Biol 1996; 8: 731–8. CrossRef
- Ciambrone GJ, McKeown-Longo PJ. Plasminogen activator inhibitor type I stabilized vitronectin-dependent adhesion in HT1080 cells. J Cell Biol 1990; 111: 2183–95. CrossRef
- Waltz DA, Chapman HA. Reversible cellular adhesion to vitronectin linked to urokinase receptor occupancy. J Biol Chem 1994; 269: 14746–50.
- Cubellis MV, Andreasen P, Ragno P, Mayer M, Dano K, Blasi F. Accessibility of receptor-bound urokinase to type-1 plasminogen activator inhibitor. Proc Natl Acad Sci USA 1989; 86: 4828–32. CrossRef
- Pollanen J, Vaheri A, Tapiovaara H et al. Prourokinase activation on the surface of human rhabdomyosarcoma cells: Localization and inactivation of newly formed urokinase-type plasminogen activator by recombinant class 2 plasminogen activator inhibitor. Proc Natl Acad Sci USA 1990; 87: 2230–4. CrossRef
- Danø K, Andreasen IA, GrØndal-Hansen J et al. Plasminogen activators tissue degradation and cancer. Adv Cancer Res 1985; 44: 139–266. CrossRef
- Mackay AR, Hartlzer JL, Pelina M, Thorgeirsson UP. Studies on the ability of 65 kDa and 92 kDa tumor cell gelatinases to degrade type IV collagen. J Biol Chem 1990; 265: 21929–34.
- Hoosein NM, Boyd DD, Hollas WJ et al. Involvement of urokinase and its receptor in the invasiveness of human prostatic carcinoma cell lines. Cancer Comm 1991; 3: 255–64.
- Mackay AR, Ballin M, Pelina MD et al. Effect of phorbol ester and cytokines on matrix metalloproteinases and tissue inhibitor of metalloproteinase expression in tumor and normal cell lines. Invas Metast 1992; 12: 168–84.
- Festuccia C, Dolo V, Guerra F et al. Plasminogen activator system modulates invasive capacity and proliferation in prostatic tumor cells. Clin Exp Metastasis 1998; 16: 513–28. CrossRef
- Taylor DD, Black PH. Shedding of plasma membrane fragments. Neoplastic and developmental importance. In Steinberg M (ed): Developmental Biology. New York: Plenum Press 1986; 33–57.
- Dolo V, D'Ascenzo S, Violini S et al. Matrix-degrading proteinases are shed in membrane vesicles by ovarian cancer cells in vivo and in vitro. Clin Exp Metastasis 1999; 17: 131–40. CrossRef
- Van Blitterswijk WJ, Dever G, Krol J, Emmelot P. Comparative lipid analysis of purified plasma membranes and shed extracellular membrane vesicles from normal murine thymocytes and leukemia GSRL cells. Biochem Biophys Acta 1986; 688: 495–504.
- Dolo V, Ginestra A, Ghersi G et al. Human breast carcinoma cells cultured in the presence of serum shed membrane vesicles rich in gelatinolytic activities. J Submicrosc Cytol Pathol 1994; 26: 173–80.
- Ginestra A, Monea S, Seghezzi G et al. Urokinase plasminogen activator and gelatinases are associated with membrane vesicles shed by human HT1080 fibrosarcoma cells. J Biol Chem 1997; 272: 17216–21. CrossRef
- Dolo V, Ginestra A, Cassarà D et al. Selective localization of matrix metalloproteinase 9, βl integrins, and human lymphocyte antigen class I molecules on membrane vesicles shed by 8701-BC breast carcinoma cells. Cancer Res 1998; 58: 4468–74.
- Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–54. CrossRef
- Nakajima M, Welch DR, Belloni PN et al. Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res 1987; 47: 4869–76.
- Albini A, Iwamoto Y, Kleinman HK et al. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 1987; 47: 3239–45.
- Dolo V, Adobati E, Canevari S et al. Membrane vesicles shed into extracellular medium by human breast carcinoma cells carry tumorassociated surface antigens. Clin Exp Metastasis 1995; 13: 277–86. CrossRef
- Poste G, Nicolson GL. Arrest and metastasis of blood-borne tumor cells are modified by fusion of plasma membrane vesicles from highly metastatic cells. Proc Natl Acad Sci USA 1980; 77: 399–403. CrossRef
- Ginestra A, Miceli D, Dolo V et al. Membrane vesicles in ovarian cancer fluids: A new potential marker. Anticancer Res 1999; 19: 3439–45.
- Ellis V, Scully M, Kakkar VV. Plasminogen activation initiated by single chain urokinase type plasminogen activator. Potentiation by U937 monocytes. J Biol Chem 1989; 264: 2184–8.
- Festuccia C, Vicentini C, di Pasquale AB et al. Plasminogen activator activities in short-term tissue cultures of benign prostatic hyperplasia and prostatic carcinoma. Oncol Res 1995; 7: 131–8.
- Murphy G, Stanton H, Cowell S et al. Mechanisms for pro-matrix metalloproteinase activation. APMIS 1999; 107: 38–44. CrossRef
- Yebra M, Parry GCN, Stromblad S et al. Requirement of receptorbound urokinase-type plasminogen activator for integrin alphavbeta5-directed cell migration. J Biol Chem 1996; 271: 29393–9. CrossRef
- Martin GR, Timpl R. Laminin and other basement membrane components. Annu Rev Cell Biol 1987; 3: 57–85. CrossRef
- Iwamoto Y, Graf J, Sasaki M et al. A synthetic pentapeptide from the B1 chain of laminin is chemotactic for B16F10 melanoma cells. J Cell Physiol 1988; 134: 287–91. CrossRef
- Vesicle-associated urokinase plasminogen activator promotes invasion in prostate cancer cell lines
Clinical & Experimental Metastasis
Volume 18, Issue 2 , pp 163-170
- Cover Date
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- Online ISSN
- Kluwer Academic Publishers
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- membrane vesicles
- prostate cancer
- tumor invasion
- urokinase plasminogen activator
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