The Crosstalk between Cancer Stem Cells and Microenvironment Is Critical for Solid Tumor Progression: The Significant Contribution of Extracellular Vesicles

Abstract

Several evidences nowadays demonstrated the critical role of the microenvironment in regulating cancer stem cells and their involvement in tumor progression. Extracellular vesicles (EVs) are considered as one of the most effective vehicles of information among cells. Accordingly, a number of studies led to the recognition of stem cell-associated EVs as new complexes able to contribute to cell fate determination of either normal or tumor cells. In this review, we aim to highlight an existing bidirectional role of EV-mediated communication-from cancer stem cells to microenvironment and also from microenvironment to cancer stem cells-in the most widespread solid cancers as prostate, breast, lung, and colon tumors.

Figure 1

The graph shows the number of publication recorded in PubMed in the last 10 years (up to June 2018), by typing the following: 1st bar: extracellular vesicles “and” cancer (prostate, breast, lung, and colon) as well as extracellular vesicles “and” cancer “and” stemness; 2nd bar: exosomes “and” cancer (prostate, breast, lung, and colon) NOT extracellular vesicles as well as exosomes “and” cancer “and” stemness NOT extracellular vesicles; 3rd bar: microvesicles “and” cancer (prostate, breast, lung, and colon) NOT extracellular vesicles as well as microvesicles “and” cancer “and” stemness NOT extracellular vesicles.

Figure 2

Specific interaction between microenvironment/metastatic niche components (i.e., fibroblasts, adipocytes, and macrophages) and organ-specific tumor cells through EVs, described in detail in the text. Tumor spheres are representative of a CSC-enriched tumor compartment, while tumor cells indicated a differentiated compartment. Green arrows indicated EV-mediated signals from microenvironment to tumor, blue arrows indicated EV-mediated signals from tumor to microenvironment, and light pink arrows indicated autocrine signaling mediated by EVs from tumor cells to the tumor sphere and vice versa.