Cancer stem cell-derived exosome-induced metastatic cancer: An orchestra within the tumor microenvironment.

Although the mechanisms as well as pathways associated with cancer stem cell (CSC) maintenance, expansion, and tumorigenicity have been extensively studied and the role of tumor cell (TC)-derived exosomes in this process is well understood, there is a paucity of research focusing specifically on the functional mechanisms of CSC-derived exosomes (CSC-Exo)/-exosomal-ncRNAs and their impact on malignancy. This shortcoming needs to be addressed, given that these vesicular and molecular components of CSCs could have a great impact on the cancer initiation, progression, and recurrence through their interaction with other key tumor microenvironment (TME) components, such as MSCs/MSC-Exo and CAFs/CAF-Exo. In particular, understanding CSCs/CSC-Exo and its crosstalk with MSCs/MSC-Exo or CAFs/CAF-Exo that are associated with the proliferation, migration, differentiation, angiogenesis, and metastasis through an enhanced process of self-renewal, chemotherapy as well as radiotherapy resistance may aid cancer treatment. This review contributes to this endeavor by summarizing the characteristic features and functional mechanisms of CSC-Exo/MSC-Exo/CAF-Exo and their mutual impact on cancer progression and therapy resistance. [Display omitted] • Cancer stem cell (CSC) play a crucial role in TME-induced cancer progression. • Enhanced activation of various signalings in CSCs make them highly resistant subpopulation. • One of the major reasons of low onco-therapeutic efficacy is the dormant/quiescent state of CSCs. • The release of exosomes (Cexosomes) and exomiRs (CexomiRs) from CSCs are the two emerging key culprits involved in tumorigenesis. • Cexosomes and CexomiRNAs could be the key targets to treat CSC-mediated metastatic cancer. [ABSTRACT FROM AUTHOR]