Molecular Mechanisms of Tumor Promoting Breast Fibroblasts.
Rudnick, Jenny.
2011
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Abstract: Breast cancer is a heterogeneous, multi-factorial disease of aberrant breast development whose etiology relies upon several microenvironmental changes within the tissue. As cancerous cells accumulate within the breast epithelium, fibroblasts within the connective tissue stroma become activated, thereby inducing inflammation, matrix remodeling, and bone marrow derived cell recruitment, wh... read moreich collectively promote tumor growth. Fibroblasts within breast tumor tissues are heterogeneous, and cell surface markers or functional characteristics of the most tumor promoting fibroblasts within the cell population remain ill-defined. Moreover, the molecular mechanisms governing the gene expression of tumor promoting fibroblasts, in comparison to fibroblasts from disease free breast tissues, remain largely unknown. Here, I demonstrate that tumor promoting fibroblasts are distinguished from those that are non-tumor promoting based on their high secretion of the pro-inflammatory hormone prostaglandin E2 (PGE2) and their response to PGE2 signaling. PGE2 signaling enhances fibroblast secretion of interleukin 6 (IL-6), which is required for the expansion of breast cancer stem-like cells (BCSCs). Secondly, I demonstrate that fibroblasts isolated from stroma of breast carcinomas, referred to as cancer associated fibroblasts (CAFs), are distinguished from fibroblasts isolated from disease free reduction mammoplasty tissues (RMFs) based on their ability to induce the expression of mature microRNA21 (miR21) in response to TGF. Collectively, these data may provide foundations for discovery of adjuvant breast cancer therapies targeting tumor associated stroma and insight into patients who may benefit best from this additional treatment option.
Thesis (Ph.D.)--Tufts University, 2011.
Submitted to the Dept. of Cell, Molecular & Developmental Biology.
Advisor: Charlotte Kuperwasser.
Committee: Grace Gill, Phillip Hinds, Jonathan Garlick, and Carla Kim.
Keywords: Cellular biology, Biology, and Health sciences.read less - ID:
- mp48sr23b
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