The impact of extracellular vesicles on breast cancer metastasis and therapeutics: genetic considerations
Leila Jahangiri
Abstract
• The four breast cancer subtypes exhibited specific exosome content. • More aggressive cells tended to secrete extracellular vesicles with high matrix metalloprotease content. • Exosomes from breast cancer cells lowered metabolism in neighbouring T cells. • FOXM1-loaded exosomes released by breast cancer cells triggered M2 macrophage polarisation. • Inhibiting exosome release by breast cancer cells enhanced sensitivity to chemotherapy. Breast cancer is a significant health problem across the world, and a better understanding of the cellular and molecular properties of the microenvironment in which the breast cancer cells reside is paramount. Breast cancer cells exhibit an intricate bilateral interaction with the tumour microenvironment, which can contribute to tumour progression. This tumour microenvironment comprises a host of proteins, proteoglycans, glycoproteins, signalling molecules, stromal and immune cells, in addition to extracellular vesicles. Extracellular vesicles encompass a range of vesicles that facilitate cell-to-cell communication and signal relay. Examples of these extracellular vesicles include microvesicles, exosomes and apoptotic bodies. Other categorisations divide extracellular vesicles into exosomes and ectosomes based on their biogenesis. The content of extracellular vesicles can be DNA, RNA, miRNA, proteins, glycans and lipids. This content can affect the tumour microenvironment and tumour metastasis and progression. As such, this review article aims to understand the content of extracellular vesicles and those that promote invasion and metastasis in the context of the tumour microenvironment. The implications of these extracellular vesicles for breast cancer therapeutics will be addressed. Finally, the genes indicated in these processes will be discussed.