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].
|Citazione:||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].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence|
|Autori:||Bifulco, K; Votta, G; Ingangi, V; Di Carluccio, G; Rea, D; Losito, S; Montuori, N; Ragno, P; Stoppelli, M; Arra, C; Carriero, M|
VOTTA, GIUSEPPINA (Secondo)
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.18632/oncotarget.1930|
|Appare nelle tipologie:||01 - Articolo su rivista|