Effects of conjugated linoleic acid on stromal cells in the mammary gland
Wagner, Katherine Elizabeth
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Stromal cells represent a novel target for chemopreventively modifying the breast microenvironment. The purpose of these studies was to test the hypothesis that conjugated linoleic acid (CLA) acts chemoprotectively against mammary tumorigenesis through effects on stromal cells. Proliferation of resting and senescent fibroblasts was decreased by CLA; cell-cycle arrest proteins p16, p53, and gadd45 appeared to be increased, by immunofluorescent staining. In vivo, stromal remodeling by CLA was not associated with inflammation, as smooth muscle actin positive myofibroblasts were not seen in the mouse mammary fibrocellular stroma, after one or seven weeks of CLA supplementation. Proteomic analysis using 2D-DIGE identified increased annexin A, and decreased c-MET protein, in response to 9,11-CLA. The ability of CLA to alter both resting and senescent stromal cells in a chemopreventive manner, in the absence of myofibrosis in vivo, suggests that CLA represents a multipotent stromal modifying agent which acts without induction of inflammatory fibrosis.