title: Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence.
abstract: The clinical relevance of the urokinase receptor (uPAR) as a prognostic marker in ovarian cancer is well documented. We had shown that the uPAR sequence corresponding to 84-95 residues, linking D1 and D2 domains (uPAR84-95), drives cell migration and angiogenesis in a protease-independent manner. This study was aimed at defining the contribution of uPAR84-95 sequence to invasion of ovarian cancer cells. Now, we provide evidence that the ability of uPAR-expressing ovarian cancer cells to cross extra-cellular matrix and mesothelial monolayers is prevented by specific inhibitors of the uPAR84-95 sequence. To specifically investigate uPAR84-95 function, uPAR-negative CHO-K1 cells were stably transfected with cDNAs coding for uPAR D2 and D3 regions exposing (uPARD2D3) or lacking (uPAR∆D2D3) the 84-95 sequence. CHO-K1/D2D3 cells were able to cross matrigel, mesothelial and endothelial monolayers more efficiently than CHO-K1/∆D2D3 cells, which behave as CHO-K1 control cells. When orthotopically implanted in nude mice, tumor nodules generated by CHO-K1/D2D3 cells spreading to peritoneal cavity were more numerous as compared to CHO-K1/∆D2D3 cells. Ovarian tumor size and intra-tumoral microvessel density were significantly reduced in the absence of uPAR84-95. Our results indicate that cell associated uPAR promotes growth and abdominal dissemination of ovarian cancer cells mainly through its uPAR84-95 sequence.
authors: Department of Experimental Oncology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
authors: Katia
authors: K
authors: Bifulco
authors: Department of Experimental Pathology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
authors: Giuseppina
authors: G
authors: Votta
authors: Department of Experimental Oncology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
authors: Vincenzo
authors: V
authors: Ingangi
authors: Department of Experimental Oncology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
authors: Gioconda
authors: G
authors: Di Carluccio
authors: Department of Experimental Oncology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
authors: Domenica
authors: D
authors: Rea
authors: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", National Research Council, Naples, Italy.
authors: Simona
authors: S
authors: Losito
authors: Department of Translational Medical Sciences,''Federico II'' University, Naples, Italy.
authors: Nunzia
authors: N
authors: Montuori
authors: Department of Chemistry and Biology, University of Salerno, Fisciano (Salerno), Italy.
authors: Pia
authors: P
authors: Ragno
authors: Department of Experimental Pathology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
authors: Maria Patrizia
authors: MP
authors: Stoppelli
authors: Department of Experimental Oncology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy. These authors contributed equally.
authors: Claudio
authors: C
authors: Arra
authors: Department of Experimental Oncology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy. These authors contributed equally.
authors: Maria Vincenza
authors: MV
authors: Carriero
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics*; D011379:Prognosis; D055293:Receptors, Urokinase Plasminogen Activator; D014162:Transfection
chemical_list: D055293:Receptors, Urokinase Plasminogen Activator