Human breast fibroblasts inhibit growth of the MCF10AT xenograft model of proliferative breast disease

Andrea Sadlonova, Shibani Mukherjee, Damon B. Bowe, Sandra R. Gault, Nicole A. Dumas, Brian A. Van Tine, Natalya Frolova, Grier P. Page, Danny R. Welch, Lea Novak, Andra R. Frost

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Stromal fibroblasts are important for normal breast homeostasis and regulation of epithelial growth; however, this regulatory function is altered during carcinogenesis. To study the role of fibroblasts in the development of breast cancer, fibroblasts derived from normal breast (NAFs) were incorporated into the MCF10AT xenograft model of progressive proliferative breast disease. The persistence of human NAFs in xenografts was established by intracellular labeling and tyramide-coupled fluorescent in situ hybridization. Overall, the number of MCF10AT epithelial structures was decreased, and the rate of epithelial cell apoptosis was increased in xenografts containing NAFs. However, these changes were primarily in low-grade epithelial structures, corresponding to normal or mildly hyperplastic ductal epithelium. The level and rate of apoptosis of high-grade epithelial structures, corresponding to in situ and invasive carcinoma, were not consistently altered by NAFs. In addition, there was variability in the growth-inhibitory capacity of NAFs derived from different individuals. NAFs induced changes in the morphology of high-grade MCF10AT structures and in xenograft stroma, including the composition of extracellular matrix, and increased angiogenesis and lymphocytic infiltration. These findings imply that NAFs can inhibit the growth of normal and hyperplastic epithelium but are less able to regulate the more transformed epithelial cells that arise during carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1064-1076
Number of pages13
JournalAmerican Journal of Pathology
Volume170
Issue number3
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Human breast fibroblasts inhibit growth of the MCF10AT xenograft model of proliferative breast disease'. Together they form a unique fingerprint.

  • Cite this

    Sadlonova, A., Mukherjee, S., Bowe, D. B., Gault, S. R., Dumas, N. A., Van Tine, B. A., Frolova, N., Page, G. P., Welch, D. R., Novak, L., & Frost, A. R. (2007). Human breast fibroblasts inhibit growth of the MCF10AT xenograft model of proliferative breast disease. American Journal of Pathology, 170(3), 1064-1076. https://doi.org/10.2353/ajpath.2007.060031