+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Interactions between exosomes from breast cancer cells and primary mammary epithelial cells leads to generation of reactive oxygen species which induce DNA damage response, stabilization of p53 and autophagy in epithelial cells



Interactions between exosomes from breast cancer cells and primary mammary epithelial cells leads to generation of reactive oxygen species which induce DNA damage response, stabilization of p53 and autophagy in epithelial cells



Plos one 9(5): E97580



Exosomes are nanovesicles originating from multivesicular bodies and are released by all cell types. They contain proteins, lipids, microRNAs, mRNAs and DNA fragments, which act as mediators of intercellular communications by inducing phenotypic changes in recipient cells. Tumor-derived exosomes have been shown to play critical roles in different stages of tumor development and metastasis of almost all types of cancer. One of the ways by which exosomes affect tumorigenesis is to manipulate the tumor microenvironments to create tumor permissive "niches". Whether breast cancer cell secreted exosomes manipulate epithelial cells of the mammary duct to facilitate tumor development is not known. To address whether and how breast cancer cell secreted exosomes manipulate ductal epithelial cells we studied the interactions between exosomes isolated from conditioned media of 3 different breast cancer cell lines (MDA-MB-231, T47DA18 and MCF7), representing three different types of breast carcinomas, and normal human primary mammary epithelial cells (HMECs). Our studies show that exosomes released by breast cancer cell lines are taken up by HMECs, resulting in the induction of reactive oxygen species (ROS) and autophagy. Inhibition of ROS by N-acetyl-L-cysteine (NAC) led to abrogation of autophagy. HMEC-exosome interactions also induced the phosphorylation of ATM, H2AX and Chk1 indicating the induction of DNA damage repair (DDR) responses. Under these conditions, phosphorylation of p53 at serine 15 was also observed. Both DDR responses and phosphorylation of p53 induced by HMEC-exosome interactions were also inhibited by NAC. Furthermore, exosome induced autophagic HMECs were found to release breast cancer cell growth promoting factors. Taken together, our results suggest novel mechanisms by which breast cancer cell secreted exosomes manipulate HMECs to create a tumor permissive microenvironment.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053906353

Download citation: RISBibTeXText

PMID: 24831807

DOI: 10.1371/journal.pone.0097580


Related references

Role of p53 and reactive oxygen species in apoptotic response to copper and zinc in epithelial breast cancer cells. Apoptosis 10(1): 111-121, 2005

DNA damage by reactive oxygen species in human breast epithelial cells. FASEB Journal 16(4): A532, 2002

Airborne quinones induce cytotoxicity and DNA damage in human lung epithelial A549 cells: the role of reactive oxygen species. Chemosphere 100: 42-49, 2014

Expression of mutant K-ras in lung epithelial cells increases generation of reactive oxygen species and oxidative DNA damage. Proceedings of the American Association for Cancer Research Annual Meeting 43: 868, 2002

Catechol metabolites of endogenous estrogens induce redox cycling and generate reactive oxygen species in breast epithelial cells. Carcinogenesis 32(8): 1285-1293, 2011

Reactive oxygen species induce antiviral innate immune response through IFN-λ regulation in human nasal epithelial cells. American Journal of Respiratory Cell and Molecular Biology 49(5): 855-865, 2013

Diesel exhaust particles induce an inflammatory response in airway epithelial cells: Involvement of reactive oxygen species. Biofactors 16(1-2): 15-17, 2002

Advanced glycation end products induce human corneal epithelial cells apoptosis through generation of reactive oxygen species and activation of JNK and p38 MAPK pathways. Plos one 8(6): E66781, 2013

Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells. Journal of Natural Medicines 69(4): 522-530, 2015

Jaceosidin induces apoptosis in ras-transformed human breast epithelial cells through generation of reactive oxygen species. Annals of the new York Academy of Sciences 1095: 483-495, 2007

Mobilization of iron from urban particulates leads to generation of reactive oxygen species in vitro and induction of ferritin synthesis in human lung epithelial cells. Chemical Research in Toxicology 10(7): 828-834, 1997

Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species. Plos one 7(9): E44132, 2012

Benzo pyrene metabolites induce Epidermal Growth Factor Receptor -dependent cell signaling in human mammary epithelial cells A potential role for reactive oxygen species. Proceedings of the American Association for Cancer Research Annual Meeting 43: 1035, 2002

Psoralidin induced reactive oxygen species (ROS)-dependent DNA damage and protective autophagy mediated by NOX4 in breast cancer cells. Phytomedicine 23(9): 939-947, 2016

Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes and Development 15(1): 65, 2001