Paradoxical antiproliferative effect by a murine mammary tumor-derived epithelial cell line

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dc.contributor.author Gurzov, Esteban N.
dc.contributor.author Nabha, Sanaa M.
dc.contributor.author Yamamoto, Hamilto
dc.contributor.author Meng, Hong
dc.contributor.author Scharovsky, O. Graciela
dc.contributor.author Bonfil, R. Daniel
dc.date.accessioned 2012-07-12T21:06:55Z
dc.date.available 2012-07-12T21:06:55Z
dc.date.issued 2007-10-01
dc.identifier.issn 1471-240
dc.identifier.uri http://hdl.handle.net/2133/1938
dc.description.abstract Background Despite significant advancement in breast cancer therapy, there is a great need for a better understanding of the mechanisms involved in breast carcinogenesis and progression, as well as of the role of epigenetic contributions from stromal cells in mammary tumorigenesis. In this study, we isolated and characterized murine mammary tumor-derived epithelial and myofibroblast cell lines, and investigated the in vitro and in vivo effect of cellular soluble factors produced by the epithelial cell line on tumor cells. Methods Morphology, immunophenotype, cytogenetics, invasiveness, and tumorigenicity of epithelial (LM-234ep) and myofibroblast (LM-234mf) cell lines isolated from two murine mammary adenocarcinomas with common ancestor were studied. The in vitro effects of LM-234ep conditioned medium on proliferation, cell cycle distribution, and expression of cell cycle proteins, were investigated in LM-234mf cells, mouse melanoma cells (B16-F10), and human cervical adenocarcinoma cells (HeLa). The in vivo anti-tumor activity of LM-234ep conditioned media was evaluated in subcutaneous tumors formed in nude mice by B16-F10 and HeLa cells. Results LM-234ep cells were found to be cytokeratin positive and hipertriploid, whereas LM-234mf cells were α-smooth muscle actin positive and hypohexaploid. Chromosome aberrations were found in both cases. Only LM-234mf revealed to be invasive in vitro and to secrete active MMP-2, though neither of the cell types were able to produce progressing tumors. LM-234ep-derived factors were able to inhibit the in vitro growth of LM-234mf, B16-F10, and HeLa cells, inducing cell cycle arrest in G0/G1 phase. The administration of LM-234ep conditioned medium inhibited the growth of B16-F10 and HeLa tumors in nude mice. Conclusion Our data suggest the existence of epithelial cell variants with tumor suppressive properties within mammary tumors. To our knowledge, this is the first report showing antiproliferative and antineoplastic activities induced by tumor-derived epithelial cells. es
dc.format application/pdf
dc.language.iso en es
dc.publisher BioMed Central es
dc.rights openAccess
dc.subject.mesh Actins/metabolism
dc.subject.mesh Adenocarcinoma/genetics
dc.subject.mesh Adenocarcinoma/metabolism
dc.subject.mesh Animals
dc.subject.mesh Carcinogenicity Tests
dc.subject.mesh Cell Line, Tumor
dc.subject.mesh Cell Proliferation
dc.subject.mesh Chromosome Aberrations
dc.subject.mesh Culture Media, Conditioned
dc.subject.mesh Epithelial Cells/metabolism
dc.subject.mesh Female
dc.subject.mesh Gelatinases/metabolism
dc.subject.mesh Humans
dc.subject.mesh Keratins/metabolism
dc.subject.mesh Mammary Neoplasms, Experimental/genetics
dc.subject.mesh Mammary Neoplasms, Experimental/metabolism
dc.subject.mesh Melanoma/metabolism
dc.subject.mesh Mice
dc.subject.mesh Mice, Inbred BALB C
dc.subject.mesh Paracrine Communication
dc.subject.mesh Uterine Cervical Neoplasms/metabolism
dc.title Paradoxical antiproliferative effect by a murine mammary tumor-derived epithelial cell line es
dc.type article
dc.type artículo
dc.type publishedVersion
dc.description.peerreviewed Peer reviewed es
dc.relation.publisherversion http://www.biomedcentral.com/1471-2407/7/184 es
dc.rights.text © 2007 Gurzov et al; licensee BioMed Central Ltd. es


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