Cancer-Associated Fibroblasts: Building Blocks of the Tumor Stroma

Cancer-Associated Fibroblasts (CAFs) are one of the most abundant cells in the stromal region of most solid tumors. CAFs are considered as the main source for the production of extracellular matrix in the tumor stroma. Differentiation and multiplication of CAFs is directly correlated with cancer aggressiveness and relapse chances as obviously reported in case of the highly desmoplastic pancreatic ductal adenocarcinoma. The Extracellular Matrix (ECM) constitutes the major part of the tumor stroma, and is defined as the non-cellular, intercellular component of the tumor stroma. ECM carries key physiological functions within tissues such as cellular adhesion, cell–cell crosstalk, and cell differentiation. Interestingly, in combination with gemcitabine, calcipotriol, a vitamin D3 analogue has been shown to reprogram the tumor stroma and promote gemcitabine intratumoral accumulation, lowered tumor volume, and reduced mortality in pancreatic cancer murine model. Interestingly, metformin, an anti-diabetic drug, and arsenic trioxide were found to restore cancer cells sensitivity to tamoxifen in breast cancer cells.