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Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence
The clinical relevance of the urokinase receptor (uPAR) as a prognostic marker in ovarian cancer is well documented. We have shown that the uPAR sequence corresponding to 84-95 residues, linking D1 and D2 domains (uPAR(84-95)), drives cell migration and angiogenesis in a protease-independent manner....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147313/ https://www.ncbi.nlm.nih.gov/pubmed/24980826 |
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author | Bifulco, Katia Votta, Giuseppina Ingangi, Vincenzo Carluccio, Gioconda Di Rea, Domenica Losito, Simona Montuori, Nunzia Ragno, Pia Stoppelli, Maria Patrizia Arra, Claudio Carriero, Maria Vincenza |
author_facet | Bifulco, Katia Votta, Giuseppina Ingangi, Vincenzo Carluccio, Gioconda Di Rea, Domenica Losito, Simona Montuori, Nunzia Ragno, Pia Stoppelli, Maria Patrizia Arra, Claudio Carriero, Maria Vincenza |
author_sort | Bifulco, Katia |
collection | PubMed |
description | The clinical relevance of the urokinase receptor (uPAR) as a prognostic marker in ovarian cancer is well documented. We have shown that the uPAR sequence corresponding to 84-95 residues, linking D1 and D2 domains (uPAR(84-95)), drives cell migration and angiogenesis in a protease-independent manner. This study is aimed at defining the contribution of uPAR(84-95) 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 PAR(84-95) sequence. To specifically investigate uPAR(84-95) function, uPAR-negative CHO-K1 cells were stably transfected with cDNAs coding for uPAR D2 and D3 regions and 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 uPAR(84-95). Our results indicate that cell associated uPAR promotes growth and abdominal dissemination of ovarian cancer cells mainly through its uPAR(84-95) sequence. |
format | Online Article Text |
id | pubmed-4147313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-41473132014-08-29 Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence Bifulco, Katia Votta, Giuseppina Ingangi, Vincenzo Carluccio, Gioconda Di Rea, Domenica Losito, Simona Montuori, Nunzia Ragno, Pia Stoppelli, Maria Patrizia Arra, Claudio Carriero, Maria Vincenza Oncotarget Research Paper The clinical relevance of the urokinase receptor (uPAR) as a prognostic marker in ovarian cancer is well documented. We have shown that the uPAR sequence corresponding to 84-95 residues, linking D1 and D2 domains (uPAR(84-95)), drives cell migration and angiogenesis in a protease-independent manner. This study is aimed at defining the contribution of uPAR(84-95) 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 PAR(84-95) sequence. To specifically investigate uPAR(84-95) function, uPAR-negative CHO-K1 cells were stably transfected with cDNAs coding for uPAR D2 and D3 regions and 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 uPAR(84-95). Our results indicate that cell associated uPAR promotes growth and abdominal dissemination of ovarian cancer cells mainly through its uPAR(84-95) sequence. Impact Journals LLC 2014-05-01 /pmc/articles/PMC4147313/ /pubmed/24980826 Text en Copyright: © 2014 Bifulco et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Bifulco, Katia Votta, Giuseppina Ingangi, Vincenzo Carluccio, Gioconda Di Rea, Domenica Losito, Simona Montuori, Nunzia Ragno, Pia Stoppelli, Maria Patrizia Arra, Claudio Carriero, Maria Vincenza Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence |
title | Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence |
title_full | Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence |
title_fullStr | Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence |
title_full_unstemmed | Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence |
title_short | Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence |
title_sort | urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147313/ https://www.ncbi.nlm.nih.gov/pubmed/24980826 |
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