The multifaceted role of extracellular vesicles in metastasis: Priming the soil for seeding

Abstract

Extracellular vesicles (EVs), including exosomes, play a key role in inter and intracellular communication, promoting the proliferation and invasion of recipient cells to support tumor growth and metastasis. Metastasis comprises multiple steps that first include the detachment of tumor cells through epithelial to mesenchymal transition (EMT), allowing the physical dissemination to distant organs. Thereafter, cancer-derived exosomes are still critical components for preparing the tumor microenvironment by (i) enabling tumor cells to escape from the immunological surveillance and (ii) arranging the pre-metastatic site for the engraftment of detached cancer cells. In this review, we discuss the multifaceted role of EVs in the multiple steps of metastasis. Future research directions draw attention to EVs as biological targets for cancer diagnosis, prognosis and therapy. However, due to their significant role in cell communication, they may become a valuable drug delivery system.

Characterization of triple‐negative breast cancer preclinical models provides functional evidence of metastatic progression

“…Exosomes have emerged as regulators of intercellular and intracellular communication and can “tailor” the premetastatic niche for engraftment of cancer cells . Interestingly, the 4T1 model displayed significantly increased circulating blood exosomes at D3, simultaneous with the first evidence of lung metastasis, suggesting its active role in lung metastasis establishment . However, we did not find any modulation in exosome levels in MDA‐MB‐231‐Luc.…”

Intercellular transfer of HLA‐G: its potential in cancer immunology

“…By intercellular transfer of surface proteins, donor cancer cells can modulate the activity of recipient cells and play important roles in tumorigenesis, growth, metastasis and even drug resistance. Moreover, cancer cells using intercellular transfer of cell‐surface proteins also play critical roles in re‐shaping the tumor microenvironment to support their expansion and metastatic activity, as well as dampen antitumor immune responses . In this context, a recent study by Hamieh et al .…”

“…Moreover, cancer cells using intercellular transfer of cell-surface proteins also play critical roles in re-shaping the tumor microenvironment to support their expansion and metastatic activity, as well as dampen antitumor immune responses. 15,16 In this context, a recent study by Hamieh et al 17 revealed that both CD19 and CD22 expressed on NALM6 acute lymphoblastic leukaemia cells could be transferred to chimeric antigen receptor (CAR)-T cells through the process of trogocytosis. Consequently, the density of the target molecules CD19 and CD22 was decreased on the tumor cells, and the T-cell killing activity was abated by the fratricide and exhaustion of the T cells with molecules acquired target by trogocytosis by CAR-T cells.…”

Mechanisms of Drug Resistance in Cancer: The Role of Extracellular Vesicles

“…It is also noteworthy that EVs and their content can serve as biomarkers for cancer . Given that there are changes in EV content that could mediate their ability to induce drug resistance when transferred between cells, it is logical that these changes could also serve as a biomarker for the presence of tumors that are either resistant to specific drugs or harbor the capacity to transfer resistance .…”