TY - JOUR
T1 - Human breast fibroblasts inhibit growth of the MCF10AT xenograft model of proliferative breast disease
AU - Sadlonova, Andrea
AU - Mukherjee, Shibani
AU - Bowe, Damon B.
AU - Gault, Sandra R.
AU - Dumas, Nicole A.
AU - Van Tine, Brian A.
AU - Frolova, Natalya
AU - Page, Grier P.
AU - Welch, Danny R.
AU - Novak, Lea
AU - Frost, Andra R.
N1 - Funding Information:
Supported by the National Institutes of Health (grants CA097472 and CA105950) and the National Foundation for Cancer Research.
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34247886174&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2007.060031
DO - 10.2353/ajpath.2007.060031
M3 - Article
C2 - 17322389
AN - SCOPUS:34247886174
SN - 0002-9440
VL - 170
SP - 1064
EP - 1076
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -