Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth

The successful use of transcriptional targeting for cancer therapy depends on the activity of a given promoter inside the malignant cell. Because solid human tumors evolve as a "cross-talk" between the different cell types within the tumor, we hypothesized that targeting the entire tumor m...

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Autores principales: Lopez, María V., Blanco, Patricia, Viale, Diego L., Cafferata, Eduardo G., Carbone, Cecilia, Gould, David, Chernajovsky, Yuti, Podhajcer, Osvaldo L.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2006
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83060
Aporte de:
id I19-R120-10915-83060
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
Secreted protein acidic and rich in cysteine
tumor
herpes simplex virus
melanoma
spellingShingle Ciencias Médicas
Secreted protein acidic and rich in cysteine
tumor
herpes simplex virus
melanoma
Lopez, María V.
Blanco, Patricia
Viale, Diego L.
Cafferata, Eduardo G.
Carbone, Cecilia
Gould, David
Chernajovsky, Yuti
Podhajcer, Osvaldo L.
Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth
topic_facet Ciencias Médicas
Secreted protein acidic and rich in cysteine
tumor
herpes simplex virus
melanoma
description The successful use of transcriptional targeting for cancer therapy depends on the activity of a given promoter inside the malignant cell. Because solid human tumors evolve as a "cross-talk" between the different cell types within the tumor, we hypothesized that targeting the entire tumor mass might have better therapeutic effect. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein overexpressed in different human cancers malignant melanomas both in the malignant cells compartment as in the stromal one (fibroblasts and endothelial cells). We have shown that expression of the herpes simplex virus - thymidine kinase (TK) gene driven by the SPARC promoter in combination with ganciclovir inhibited human melanoma cell growth in monolayer as well as in multicellular spheroids. This inhibitory effect was observed both in homotypic spheroids composed of melanoma cells alone as well as in spheroids made of melanoma cells and stromal cells. Expression of the TK gene was also efficient to inhibit the in vivo tumor growth of established melanomas when TK was expressed either by the malignant cells. Our data suggest that the use of therapeutic genes driven by SPARC promoter could be a valuable strategy for cancer therapy aiming to target all the cellular components of the tumor mass.
format Articulo
Articulo
author Lopez, María V.
Blanco, Patricia
Viale, Diego L.
Cafferata, Eduardo G.
Carbone, Cecilia
Gould, David
Chernajovsky, Yuti
Podhajcer, Osvaldo L.
author_facet Lopez, María V.
Blanco, Patricia
Viale, Diego L.
Cafferata, Eduardo G.
Carbone, Cecilia
Gould, David
Chernajovsky, Yuti
Podhajcer, Osvaldo L.
author_sort Lopez, María V.
title Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth
title_short Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth
title_full Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth
title_fullStr Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth
title_full_unstemmed Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth
title_sort expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (sparc) promoter in tumor or stromal cells led to the inhibition of tumor cell growth
publishDate 2006
url http://sedici.unlp.edu.ar/handle/10915/83060
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