Extracellular Vesicles as Mediators of Therapy Resistance in the Breast Cancer Microenvironment

Abstract

Resistance to various therapies, including novel immunotherapies, poses a major challenge in the management of breast cancer and is the leading cause of treatment failure. Bidirectional communication between breast cancer cells and the tumour microenvironment is now known to be an important contributor to therapy resistance. Several studies have demonstrated that crosstalk with the tumour microenvironment through extracellular vesicles is an important mechanism employed by cancer cells that leads to drug resistance via changes in protein, lipid and nucleic acid cargoes. Moreover, the cargo content enables extracellular vesicles to be used as effective biomarkers for predicting response to treatments and as potential therapeutic targets. This review summarises the literature to date regarding the role of extracellular vesicles in promoting therapy resistance in breast cancer through communication with the tumour microenvironment.

Remodeling tumor microenvironment with natural products to overcome drug resistance

“…Resistance is induced by tumor or stromal cells which secrete soluble factors in the tumor microenvironment, and the activation status of immune cells in the tumor microenvironment also affects the resistance generation ( 213 ). Extracellular vesicles represent an important mechanism for exchange bioactive molecules among cells, and changes in nucleic acid cargoes, proteins and lipids caused by the crosstalk of the tumor microenvironment and extracellular vesicles eventually lead cancer cells to acquire drug resistance ( 214 , 215 ). Cisplatin is a commonly agent utilized in many types of cancer treatment, while the tumor microenvironment has a significant effect on the generation of cisplatin resistance.…”

Extracellular vesicle cargo metabolome changes in response to the mesenchymal stromal cell microenvironment and influences cell quiescence and activation in a human breast cancer cell model

“…It has been hypothesised that the BM provides a pro-dormancy signal via, amongst other cues, paracrine events that are regulated by resident MSCs (76). Recent evidence has also supported the involvement of MSC-EVs in the onset of BCC dormancy (3,(13)(14)(15)(16)(17)(18)(19)77,78). Here, we test the hypothesis that a change in MSC phenotype, caused by aging, trauma or acute therapeutic treatment, might induce BC recurrence.…”

“…MSC-EVs carry a variety of cargoes, including the miRNAs miR-126, miR-222 and miR-342-3p, the transfer of which to BCCs is believed to inhibit breast cancer cell proliferation and/or metastasis and to induce dormancy (12)(13)(14)(15). MSC-EVs also reportedly have a dose-dependent effect on BCC migration, proliferation and adhesion in 2D and 3D spheroids in vitro, potentially via the Wnt/ b-catenin signalling pathway, initiating a more epithelial phenotype and a net loss of tumourigenicity (16)(17)(18)(19).…”

High expression of the ANXA3 gene promotes immune infiltration and improves tumor prognosis in ovarian serous carcinoma using bioinformatics analyses

“…In recent years, the immunobiological and functional research concerning EVs has made significant progress. For example, as the main component of oncosomes, tetraspanins (CD9 and CD81) function to cleave large cytoplasmic extensions from the cell body for constitutive EV secretion ( 46 ). CD63 + lysosome-related effector vesicles contain protease.…”