Differential production of angiostatin by concomitant antitumoral resistance-inducing cancer cells

The phenomenon by which tumor-bearing hosts are capable of inhibiting secondary tumor implants or metastases, known as concomitant antitumoral resistance (CAR), is presumably due to antiangiogenesis at places distant from the primary tumor. Although angiostatin, a potent inhibitor of angiogenesis, h...

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Autores principales: Binda, María Mercedes, Matar, Pablo, González, Alejandro D., Rozados, Viviana R., Gervasoni, Silvia I., Scharovsky, O. Graciela, Bonfil, R. Daniel
Formato: artículo publishedVersion article
Lenguaje:Inglés
Publicado: Wiley 2013
Materias:
Acceso en línea:http://hdl.handle.net/2133/2548
http://hdl.handle.net/2133/2548
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id I15-R121-2133-2548
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv en
topic angiostatin
concomitant antitumoral resistance
serine proteinases
metalloproteinases
angiogenesis
metastasis
spellingShingle angiostatin
concomitant antitumoral resistance
serine proteinases
metalloproteinases
angiogenesis
metastasis
Binda, María Mercedes
Matar, Pablo
González, Alejandro D.
Rozados, Viviana R.
Gervasoni, Silvia I.
Scharovsky, O. Graciela
Bonfil, R. Daniel
Differential production of angiostatin by concomitant antitumoral resistance-inducing cancer cells
topic_facet angiostatin
concomitant antitumoral resistance
serine proteinases
metalloproteinases
angiogenesis
metastasis
description The phenomenon by which tumor-bearing hosts are capable of inhibiting secondary tumor implants or metastases, known as concomitant antitumoral resistance (CAR), is presumably due to antiangiogenesis at places distant from the primary tumor. Although angiostatin, a potent inhibitor of angiogenesis, has been reported to be one of the factors responsible for suppressing the growth of secondary tumors in mice bearing previous tumors, it has not been definitively proven yet. With the aim of investigating whether CAR-inducing cancer cells display a differential angiostatin production and to support the role ascribed to that molecule concerning the inhibition of secondary tumor implants, 5 tumor models with different CAR-inducing capacities were studied herein. One of the 2 human lung cancer cell lines analyzed revealed a strong CAR against secondary s.c. tumor implants in nude mice, and 2 of 3 of the murine mammary tumors used exhibited inhibitory effect on secondary s.c. and i.v. tumor inoculations in syngeneic hosts. Since angiostatin is a proteolytic fragment from plasminogen, we examined by Western blot the ability of all conditioned media collected from the tumor cells studied to convert plasminogen to angiostatin. An association between in vivo generation of CAR and in vitro conversion of plasminogen into angiostatin was found. Since different enzymatic mechanisms were described to explain the generation of angiostatin, we also studied gelatinase and urokinase-type plasminogen activator secretion in conditioned media by zymography. The conversion of plasminogen into angiostatin by conditioned media was mainly inhibited by broad-spectrum serine proteinase inhibitors, suggesting a possible role for 1 or more enzymes of that group in the process. These findings suggest the existence of a differential angiostatin generation by CAR-inducing cancer cells, providing additional support to previous data obtained by other authors.
format artículo
publishedVersion
article
author Binda, María Mercedes
Matar, Pablo
González, Alejandro D.
Rozados, Viviana R.
Gervasoni, Silvia I.
Scharovsky, O. Graciela
Bonfil, R. Daniel
author_facet Binda, María Mercedes
Matar, Pablo
González, Alejandro D.
Rozados, Viviana R.
Gervasoni, Silvia I.
Scharovsky, O. Graciela
Bonfil, R. Daniel
author_sort Binda, María Mercedes
title Differential production of angiostatin by concomitant antitumoral resistance-inducing cancer cells
title_short Differential production of angiostatin by concomitant antitumoral resistance-inducing cancer cells
title_full Differential production of angiostatin by concomitant antitumoral resistance-inducing cancer cells
title_fullStr Differential production of angiostatin by concomitant antitumoral resistance-inducing cancer cells
title_full_unstemmed Differential production of angiostatin by concomitant antitumoral resistance-inducing cancer cells
title_sort differential production of angiostatin by concomitant antitumoral resistance-inducing cancer cells
publisher Wiley
publishDate 2013
url http://hdl.handle.net/2133/2548
http://hdl.handle.net/2133/2548
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