Exosomes in development, metastasis and drug resistance of breast cancer.
Bottom Line: Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer.However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity.This is a promising way to establish a drug delivery system.
Affiliation: The First Clinical School of Nanjing Medical University, Nanjing, China.Show MeSH
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Mentions: Exosomes transfer RNA and proteins to mediate the communication between stromal cells and cancer cells, which can influence treatment response. Exosomes transferred from stromal to breast cancer cells contribute to chemotherapy and radiation resistance through antiviral and NOTCH3 pathways.57 These exosomes increase the interferon-related DNA damage resistance signature and enhance the transcription of NOTCH target genes, thereby promoting the resistance through expanding the spectrum of therapy-resistant breast cancer cells. Release of exosomes can be promoted by hypoxia and exosomes that are associated with the radiation resistance of tumor cells under hypoxic conditions.58,30 Chronic hypoxia can alter DNA damage repair pathways and thereby induce DNA replication errors and genetic instability, which contribute to radiation resistance.59 Therefore, hypoxia-induced radiation resistance may partly be due to the delivery of exosomes. Exosomes from drug-resistant breast cancer cells transmit chemoresistance through the delivery of p-gp and miRNA.60,61 Drug-sensitive variant MCF-7 cell line (MCF-7/S) can acquire drug resistance in the presence of exosomes from docetaxel (DOC/exo)-resistant MCF-7 breast cancer cells.60 Meanwhile, p-gp expression of MCF-7/S increases and is influenced by the dose of exosomes. These results point to the fact that docetaxel-resistant breast cancer cells assimilate other breast cancer cells to acquire chemoresistance via exosome delivery of p-gp. After coculture with DOC/exo, the general resistance of MCF-7/S is enhanced and levels of some miRNAs are distinctively increased, and thereby, the general resistance of MCF-7/S is enhanced after coculture.61 In addition, DOC/exo is capable of altering gene expression in MCF-7/S. Accumulation of anticancer drugs in exosomes/vesicles that shed out of cancer cells is a drug efflux mechanism involved in drug resistance.62 Docetaxel resistance is related to the enhancement of exosome secretion in a prostate cancer model, probably due to docetaxel efflux through exosomes.63 However, this hypothesis has not been proven in any breast cancer model, and should be verified through further studies. Figure3 presents a summary diagram of exosomes in breast cancer resistance.
Affiliation: The First Clinical School of Nanjing Medical University, Nanjing, China.