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 (uPARΔD2D3) the 84-95 sequence. CHO-K1/D2D3 cells were able to cross matrigel, mesothelial and endothelial monolayers more efficiently than CHO-K1/ΔD2D3 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/ΔD2D3 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.

Bifulco, K., Votta, G., Ingangi, V., Di Carluccio, G., Rea, D., Losito, S., et al. (2014). Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence. ONCOTARGET, 5(12), 4154-4169 [10.18632/oncotarget.1930].

Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence

VOTTA, GIUSEPPINA
Secondo
;
2014

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 (uPARΔD2D3) the 84-95 sequence. CHO-K1/D2D3 cells were able to cross matrigel, mesothelial and endothelial monolayers more efficiently than CHO-K1/ΔD2D3 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/ΔD2D3 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.
Articolo in rivista - Articolo scientifico
Cell invasion; Ovarian cancer; Urokinase receptor; Oncology
English
4154
4169
16
Bifulco, K., Votta, G., Ingangi, V., Di Carluccio, G., Rea, D., Losito, S., et al. (2014). Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence. ONCOTARGET, 5(12), 4154-4169 [10.18632/oncotarget.1930].
Bifulco, K; Votta, G; Ingangi, V; Di Carluccio, G; Rea, D; Losito, S; Montuori, N; Ragno, P; Stoppelli, M; Arra, C; Carriero, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/63385
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