Tumor-Derived Osteopontin Reprograms Normal Mammary Fibroblasts to Promote Inflammation and Tumor Growth in Breast Cancer

Yoray Sharon, Yael Raz, Noam Cohen, Amir Ben-Shmuel, Hila Schwartz,

Tamar Geiger, & Neta Erez. Cancer Res. (2015) 75, 963-973.

Speaker: Yi-Chun Chen (陳怡君)                         Time: 13:10~14:00, Nov. 25, 2015

Commentator: Dr. Yan-Shen Shan (沈延盛博士)            Place: Room 601

Abstract:

    Breast cancer continues to be one of the leading causes of cancer-related deaths in women. Cancer-associated fibroblasts (CAFs) are a heterogeneous population of fibroblastic cells found in the microenvironment of solid tumors (1). Osteopontin, also known as secreted phosphoprotein 1, is an integrin-binding glyco-phosphoprotein expressed in a variety of cells and tissues (2). In this paper, the authors wanted to know how paracrine signaling from breast tumor cells reprograms normal mammary fibroblasts (NMFs). They found that breast tumor cell–secreted factors activate a proinflammatory CAF-like phenotype in NMFs. Based on the fact that osteopontin is highly expressed and secreted by breast tumor cells, they further proved that osteopontin is necessary and sufficient to activate mammary fibroblasts. Finally, the authors have revealed that osteopontin activates mammary fibroblasts via CD44 and αvβ3 to express proinflammatory genes and increases the deposition of collagen in the tumor microenvironment, thus supporting tumor growth. Taken together, tumor-secreted osteopontin plays an essential role in differentiation of normal mammary fibroblasts to proinflammatory, tumor-promoting CAFs in breast cancer.

References:

1. Walker RA. (2001) The complexities of breast cancer desmoplasia. Breast Cancer Res. 3, 143–145.

2. Anborgh PH, Mutrie JC, Tuck AB, & Chambers AF. (2010) Role of the metastasispromoting protein osteopontin in the tumour microenvironment.  J Cell Mol Med. 14, 2037-2044.