Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)
Part II. Cancer stem cells
Emerging concepts in breast tumour invasion, metastasis and therapeutic resistance emphasize the role of CSCs and their regulation by contextual signals within the tumour microenvironment. In this context, a feedback signalling loop through stromal MSCs is vital to the induction of EMT and CSC phenotypes, which are essential in invasion and metastasis. MSCs are an important source of cytokines and chemokines and their role in the plasticity of EMT/MET may depend upon tumour cell type and the presence of cell-specific receptors. The identification of EMT and MET CSC markers should facilitate future studies into the role of MSCs in regulating these cells. Protumourigenic and prometastatic functions of stromal MSCs have now been recognized in breast and other solid tumours, and it is important to understand and target this interactive signalling cascade in order to control CSC expansion and metastasis. As MSCs have the tendency to home to tumours, these cells and associated signalling networks represent attractive therapeutic targets. Although the signalling events triggered by the surrounding environments still poorly understood, targeting of abnormal tumour-promoting paracrine signals between CSCs and MSCs may be a feasible approach to the control of CSC expansion. Therefore, therapeutic strategies interfering with these pathways may provide a means of targeting CSCs, since these cells contribute to metastasis, drug resistance and poor clinical outcomes in advanced breast cancer patients.
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