Human Mesenchymal Stem Cells as Mediators of Breast Carcinoma Tumorigenesis and Progression

: mesenchymal stem cells, breast cancer, estrogen receptor, hormone independence, endocrine resistance, tumor microenvironment Breast cancer continues to be the most frequently diagnosed carcinoma in women in the U.S.[1,2] with one in eight (12%) women having the chance of developing some form of breast carcinoma over the course of their lifetime[3,4]. A tumor mass is composed of malignant cancer cells and nonmalignant benign cells. The benign cells include tumor endothelial cells, inflammatory cells, and stromal cells, as well as the extracellular matrix (ECM) that provides structural support to the malignant cells[5]. The tumor microenvironment has been shown to play an active part in tumorigenesis and cancer progression through structural support as well as secreted factors[6]. It is now understood that stromal fibroblasts within the tumor microenvironment can influence tumor cell activities, such as proliferation, survival, metastasis, and even tumor initiation[7,8,9,10,11]. The interaction between tumor cells and tumor stroma or microenvironment has been described as a two-way street, as the tumor cells influence the stroma via tissue remodeling and gene expression, and vice versa[5,12,13]. Tumor cells provide signals that stimulate