Extracellular vesicles in the treatment and diagnosis of breast cancer: a status update

Abstract

Breast cancer is one of the leading causes of cancer-related death in women. Currently, the treatment of breast cancer is limited by the lack of effectively targeted therapy and patients often suffer from higher severity, metastasis, and resistance. Extracellular vesicles (EVs) consist of lipid bilayers that encapsulate a complex cargo, including proteins, nucleic acids, and metabolites. These bioactive cargoes have been found to play crucial roles in breast cancer initiation and progression. Moreover, EV cargoes play pivotal roles in converting mammary cells to carcinogenic cells and metastatic foci by extensively inducing proliferation, angiogenesis, pre-metastatic niche formation, migration, and chemoresistance. The present update review mainly discusses EVs cargoes released from breast cancer cells and tumor-derived EVs in the breast cancer microenvironment, focusing on proliferation, metastasis, chemoresistance, and their clinical potential as effective biomarkers.

Keywords: biomarkers; breast cancer; chemoresistance; extracellular vesicles; metastasis; proliferation.

Figure 1

Roles of EVs in resistance to the treatment of breast cancer (A) Drug resistant triple-negative breast cancer cells can secrete EVs including mitochondrion (MC), miRNA (miR-423-5p, miR-887-3p) to drug sensitive triple-negative breast cancer cells. For MC, it can induce gene mutation of mtND4 to cause drug resistance. For miR-423-5p, miR-423-5p-enriched EVs could convert cisplatin-sensitive breast cancer cells into cisplatin-resistant breast cancer cells by activating proliferation, metastasis, and anti-apoptosis-related signaling pathways. For miR-887-3p, it could target BTBP7 and activate Notch/Hes1 pathway to induce drug resistance of triple-negative breast cancer cells. (B) Drug resistant luminal breast cancer cells can also secrete EVs including miR-181a-2, TRPC5, miR-9-5p to drug sensitive luminal breast cancer cells. For miR-181a-2, it can contribute to the interdiction of ER signal and activation of PI3K/AKT to induce drug resistance. TRPC5 could convert cisplatin-sensitive breast cancer cells into cisplatin-resistant breast cancer cells. For miR-9-5p, it can lead to tamoxifen treatment resistance by downregulating the expression of its target gene ADIPOQ. (C) This diminished efficacy of antibody-drug conjugate therapy may be ascribed to the binding of T-DM1 to HER2⁺ breast cancer cell-secreted exosomes, which eventually resulted in treatment resistance.