Dysregulated Jak-Stat and Wnt signaling pathways in breast tumor microenviroment.

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Increasing evidence has shown the importance of tissue microenvironment in breast tumorigenesis. The molecular contributions of stromal cells in this microenvironment, however, remain to be explored. Fibroblast is one of major cellular components in the microenvironmental moieties. In this work, we collected breast tumor-associated stromal fibroblasts from breast cancer patients, as well as normal breast fibroblasts from non-cancerous patients undergoing reduction mammoplasty. Laboratory cultivation of these stromal cells sustained fibroblasts characteristics, as demonstrated by the immunofluorescent staining with antibodies against Vimentin and Prolyl-4-hydroxylase. Global expression profiles between 7 cancer-associated and 5 control fibroblasts were evaluated by the Affymetrix U133 plus 2.0.microarray. Eighty-nine genes were identified to be differentially expressed in cancer fibroblasts relative to normal fibroblasts. These genes encode functions related to cytokines, cytokine receptors (IL13R2A, CCL2), Wnt pathway related proteins (sFRP1, sFRP4, WISP1), and cell cycle regulators (CCND2, PPAP2C). Analysis using the Pathway-Express program showed that Jak-Stat and Wnt were the two most altered signaling pathways in cancer associated fibroblasts. Thus, our data suggest that the molecular alterations of fibroblasts constitute an aberrant signaling niche in microenvironment and may in part contribute to breast cancer development.