SuPAR, a soluble form of urokinase plasminogen activator receptor, inhibits human prostate cancer cell growth and invasion

• Published in: International journal of oncology Vol. 32; no. 1; pp. 185 - 191
• Main Authors: PICCOLELLA, M, FESTUCCIA, C, MILLIMAGGI, D, LOCATELLI, A, BOLOGNA, M, MOTTA, M, DONDI, D
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 2008
• Subjects: Biological and medical sciences; Cell Line, Tumor; Cell Movement; Cell Proliferation; Extracellular Signal-Regulated MAP Kinases - metabolism; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Humans; Male; Medical sciences; Neoplasm Invasiveness; Nephrology. Urinary tract diseases; Phosphorylation; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Receptors, Cell Surface - physiology; Receptors, Urokinase Plasminogen Activator; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Human; Cell proliferation; u-Plasminogen activator; Urinary system disease; Prostate disease; Serine endopeptidases; Enzyme; metastatic progression; Malignant tumor; Soluble form; Metastasis; Invasion; Peptidases; Cancerology; soluble urokinase-type plasminogen activator receptor (suPAR); Hydrolases; Advanced stage; Inhibitor; Male genital diseases; Prostate cancer; Tumor cell; Cancer; Biological receptor
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.32.1.185

Urokinase-type plasminogen activator (uPA) and its specific membrane receptor (uPAR) control extracellular matrix proteolysis, cell migration, invasion and cell growth in several cancers. The uPAR released from human cancers is detected in blood as soluble uPAR (suPAR). No information is available on the mechanism(s) of action of suPAR on prostate cancer (PCa) cell growth and invasion. In order to clarify this issue, we tested the effect of a treatment with the human recombinant suPAR (comprising amino acids l-303) on the proliferation, migration and invasion of DU145 cells, a PCa cell line expressing a potent autocrine uPA-uPAR signalling system. The results indicate that suPAR significantly inhibits cell growth, promotes apoptosis and decreases both migration and Matrigel invasion of DU145 cells. The mechanism of action of suPAR seems to be linked to a decrease of ERK and FAK activation. Cleavage of suPAR by chymotripsin reverses these effects. When added to the uPA-negative LNCaP cells, suPAR was ineffective; on the contrary, when LNCaP cells were cultured on fibronectin-coated plates in order to stimulate uPA expression, suPAR significantly decreased cell proliferation. In conclusion, our data suggest that suPAR can function as a potent molecule scavenger for uPA in human PCa cells characterized by high levels of uPA/uPAR as in DU145 cells, while it is ineffective in uPA-deficient LNCaP cells. The molecular mechanism(s) through which suPAR participates in the control of PCa progression may bear relevance for the long-term goal to identify new therapeutic targets aimed at silencing tumours in vivo.