SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein whose overexpression in malignant or tumor-stromal cells is often associated with increased aggressiveness and bad prognosis in a wide range of human cancer types, particularly melanoma. We established the impact that ch...

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Autores principales: Prada, Federico, Benedetti, Lorena G., Bravo, Alicia I., Alvarez, Mariano J., Carbone, Cecilia, Podhajcer, Osvaldo L.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2007
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83339
Aporte de:
id I19-R120-10915-83339
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Ciencias Veterinarias
SPARC
human cancer
Melanoma
spellingShingle Ciencias Médicas
Ciencias Veterinarias
SPARC
human cancer
Melanoma
Prada, Federico
Benedetti, Lorena G.
Bravo, Alicia I.
Alvarez, Mariano J.
Carbone, Cecilia
Podhajcer, Osvaldo L.
SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth
topic_facet Ciencias Médicas
Ciencias Veterinarias
SPARC
human cancer
Melanoma
description SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein whose overexpression in malignant or tumor-stromal cells is often associated with increased aggressiveness and bad prognosis in a wide range of human cancer types, particularly melanoma. We established the impact that changes in the level of SPARC produced by malignant cells and neighboring stromal cells have on melanoma growth. Melanoma cell growth in monolayer was only slightly affected by changes in SPARC levels. However, melanoma growth in spheroids was strongly inhibited upon SPARC hyperexpression and conversely enhanced when SPARC expression was downregulated. Interestingly, SPARC overexpression in neighboring fibroblasts had no effect on spheroid growth irrespective of SPARC levels expressed by the melanoma cells, themselves. Downregulation of SPARC expression in melanoma cells induced their rejection <i>in vivo</i> through a mechanism mediated exclusively by host polymorphonuclear cells. On the other hand, SPARC hyperexpression enhanced vascular density, collagen deposition, and fibroblast recruitment in the surrounding stroma without affecting melanoma growth. In agreement with the <i>in vitro</i> data, overexpression of SPARC in co-injected fibroblasts did not affect melanoma growth <i>in vivo</i>. All the data indicate that melanoma growth is not subject to regulation by exogenous SPARC, nor by stromal organization, but only by SPARC levels produced by the malignant cells themselves.
format Articulo
Articulo
author Prada, Federico
Benedetti, Lorena G.
Bravo, Alicia I.
Alvarez, Mariano J.
Carbone, Cecilia
Podhajcer, Osvaldo L.
author_facet Prada, Federico
Benedetti, Lorena G.
Bravo, Alicia I.
Alvarez, Mariano J.
Carbone, Cecilia
Podhajcer, Osvaldo L.
author_sort Prada, Federico
title SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth
title_short SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth
title_full SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth
title_fullStr SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth
title_full_unstemmed SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth
title_sort sparc endogenous level, rather than fibroblast-produced sparc or stroma reorganization induced by sparc, is responsible for melanoma cell growth
publishDate 2007
url http://sedici.unlp.edu.ar/handle/10915/83339
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