Cancer stem cell secretome in the tumor microenvironment: a key point for an efective personalized cancer treatment

Abstract

Cancer stem cells (CSCs) represent a tumor subpopulation responsible for tumor metastasis and resistance to chemoand radiotherapy, ultimately leading to tumor relapse. As a consequence, the detection and eradication of this cell subpopulation represent a current challenge in oncology medicine. CSC phenotype is dependent on the tumor microenvironment (TME), which involves stem and diferentiated tumor cells, as well as diferent cell types, such as mesenchymal stem cells, endothelial cells, fbroblasts and cells of the immune system, in addition to the extracellular matrix (ECM), diferent in composition to the ECM in healthy tissues. CSCs regulate multiple cancer hallmarks through the interaction with cells and ECM in their environment by secreting extracellular vesicles including exosomes, and soluble factors such as interleukins, cytokines, growth factors and other metabolites to the TME. Through these fac‑ tors, CSCs generate and activate their own tumor niche by recruiting stromal cells and modulate angiogenesis, metas‑ tasis, resistance to antitumor treatments and their own maintenance by the secretion of diferent factors such as IL-6, VEGF and TGF-ß. Due to the strong infuence of the CSC secretome on disease development, the new antitumor therapies focus on targeting these communication networks to eradicate the tumor and prevent metastasis, tumor relapse and drug resistance. This review summarizes for the frst time the main components of the CSC secretome and how they mediate diferent tumor processes. Lastly, the relevance of the CSC secretome in the development of more precise and personalized antitumor therapies is discussed.