The normal mammary microenvironment suppresses the tumorigenic phenotype of mouse mammary tumor virus-neu-transformed mammary tumor cells

• Published in: Oncogene Vol. 30; no. 6; pp. 679 - 689
• Main Authors: Booth, B W, Boulanger, C A, Anderson, L H, Smith, G H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-02-2011; Nature Publishing Group
• Subjects: 631/67/1347; 631/67/1858; 631/67/327; 631/67/395; Adipose Tissue - virology; Animals; Apoptosis; Biological and medical sciences; Breast cancer; Cancer cells; Carcinoma - pathology; Carcinoma - virology; Care and treatment; Cell Biology; Cell Differentiation; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Viral; Cellular biology; Development and progression; Epithelial cells; Epithelial Cells - pathology; Epithelial Cells - virology; Epithelium; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Genetic aspects; Genotype & phenotype; Health aspects; Human Genetics; Identification and classification; Internal Medicine; Mammary gland; Mammary Glands, Animal - growth & development; Mammary Glands, Animal - pathology; Mammary Glands, Animal - virology; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - virology; Mammary Tumor Virus, Mouse; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microenvironments; Molecular and cellular biology; Mouse mammary tumor virus; Oncology; original-article; Phenotype; Phenotypes; Regeneration (Biology); Retroviridae Infections - pathology; Retroviridae Infections - virology; Rodents; Signal transduction; Transplantation; Tumor cells; Tumor Microenvironment; Tumor suppressor genes; Tumor Virus Infections - pathology; Tumor Virus Infections - virology; Tumor viruses; United States; microenvironment; suppression of tumorigenesis; mammary; erbB2/HER2; regeneration; Transformed cell; Suppression; Retroviridae; erbB2 Gene; Betaretrovirus; Normal; Carcinogenesis; Virus; Regeneration; Phenotype; C-Onc gene; Mammary gland; Mouse mammary tumor virus; Tumor cell
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2010.439

The microenvironment of the mammary gland has been shown to exert a deterministic control over cells from different normal organs during murine mammary gland regeneration in transplantation studies. When mouse mammary tumor virus (MMTV)-neu-induced tumor cells were mixed with normal mammary epithelial cells (MECs) in a dilution series and inoculated into epithelium-free mammary fat pads, they were redirected to non-carcinogenic cell fates by interaction with untransformed MECs during regenerative growth. In the presence of non-transformed MECs (50:1), tumor cells interacted with MECs to generate functional chimeric outgrowths. When injected alone, tumor cells invariably produced tumors. Here, the normal microenvironment redirects MMTV-neu-transformed tumorigenic cells to participate in the regeneration of a normal, functional mammary gland. In addition, the redirected tumor cells show the capacity to differentiate into normal mammary cell types, including luminal, myoepithelial and secretory. The results indicate that signals emanating from a normal mammary microenvironment, comprised of stromal, epithelial and host-mediated signals, combine to suppress the cancer phenotype during glandular regeneration. Clarification of these signals offers improved therapeutic possibilities for the control of mammary cancer growth.