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

Authors

Esteban N. Gurzov, Centro de Biología Molecular Severo Ochoa Universidad Autónoma de MadridFollow
Sanaa M. Nabha, Wayne State University School of Medicine and The Barbara Ann Karmanos Cancer InstituteFollow
Hamilto Yamamoto, Wayne State University School of Medicine and The Barbara Ann Karmanos Cancer InstituteFollow
Hong Meng, Wayne State University School of Medicine and The Barbara Ann Karmanos Cancer InstituteFollow
O Graciela Scharovsky, Instituto de Genética Experimental, School of Medical Sciences, University of RosarioFollow
R Daniel Bonfil, Wayne State University School of Medicine and The Barbara Ann Karmanos Cancer InstituteFollow

Document Type

Article

Abstract

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.

Disciplines

Oncology | Pathology | Urology | Women's Health

Recommended Citation

Gurzov et al. BMC Cancer 2007, 7:184
doi:10.1186/1471-2407-7-184