Generic placeholder image

Current Cancer Drug Targets


ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

Role of Exosomes in Breast Cancer Management: Evidence-Based Review

Author(s): Razan B. Al-Humaidi, Bahgat Fayed, Suleiman I. Sharif, Ayman Noreddin and Sameh S.M. Soliman*

Volume 21, Issue 8, 2021

Published on: 01 June, 2021

Page: [666 - 675] Pages: 10

DOI: 10.2174/1568009621666210601115707

Price: $65


The field of cancer research has massively grown in recent decades, leading to a better understanding of the underlying causes and greatly improving the therapeutic approaches. Breast cancer (BC) is the third leading cause of mortality among all cancers and the most common malignant disease in women worldwide, representing one in four of all cancers in women. The crosstalk between cancer cells and the surrounding microenvironment is crucial for tumor progression and metastatic process. Tumor cells communicate not only through classical paracrine signaling mechanisms, including cytokines, chemokines, growth factors, but also through “exosomes”. Exosomes are nano-vesicles that are released by various types of cells. Over the last decade, researchers have been attracted by the role of exosomes in breast cancer. It has been proven that exosomes influence major tumor-related pathways, including invasion, migration, epithelial-to-mesenchymal transition (EMT), metastasis, and drug resistance. Additionally, exosomes play important roles in clinical applications. Several studies have demonstrated the potential applications of exosomes in cancer therapy and diagnosis. Furthermore, exosomes have been engineered to function as nano-delivery systems of chemotherapeutic drugs. They can also be designed as vaccines to trigger the patient’s immune system. This review discusses the recent progress regarding the use of exosomes as drug delivery systems, therapeutic agents, biomarkers, and vaccines against breast cancer.

Keywords: Exosomes, breast cancer, therapy, biomarkers, diagnosis, vaccine.

Graphical Abstract
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[] [PMID: 30207593]
Fang, S.; Tian, H.; Li, X.; Jin, D.; Li, X.; Kong, J.; Yang, C.; Yang, X.; Lu, Y.; Luo, Y.; Lin, B.; Niu, W.; Liu, T. Clinical application of a microfluidic chip for immunocapture and quantification of circulating exosomes to assist breast cancer diagnosis and molecular classification. PLoS One, 2017, 12(4), e0175050.
[] [PMID: 28369094]
Tutanov, O.; Orlova, E.; Proskura, K.; Grigor’eva, A.; Yunusova, N.; Tsentalovich, Y.; Alexandrova, A.; Tamkovich, S. Proteomic analysis of blood exosomes from healthy females and breast cancer patients reveals an association between different exosomal bioactivity on non-tumorigenic epithelial cell and breast cancer cell migration in vitro. Biomolecules, 2020, 10(4), 495.
[] [PMID: 32218180]
Gomari, H.; Forouzandeh Moghadam, M.; Soleimani, M.; Ghavami, M.; Khodashenas, S. Targeted delivery of doxorubicin to HER2 positive tumor models. Int. J. Nanomedicine, 2019, 14, 5679-5690.
[] [PMID: 31413568]
Stevic, I.; Müller, V.; Weber, K.; Fasching, P.A.; Karn, T.; Marmé, F.; Schem, C.; Stickeler, E.; Denkert, C.; van Mackelenbergh, M.; Salat, C.; Schneeweiss, A.; Pantel, K.; Loibl, S.; Untch, M.; Schwarzenbach, H. Specific microRNA signatures in exosomes of triple-negative and HER2-positive breast cancer patients undergoing neoadjuvant therapy within the GeparSixto trial. BMC Med., 2018, 16(1), 179.
[] [PMID: 30301470]
Du, J.; Fan, J.J.; Dong, C.; Li, H.T.; Ma, B.L. Inhibition effect of exosomes-mediated Let-7a on the development and metastasis of triple negative breast cancer by down-regulating the expression of c-Myc. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(12), 5301-5314.
[PMID: 31298382]
Chaudhary, P.; Gibbs, L.D.; Maji, S.; Lewis, C.M.; Suzuki, S.; Vishwanatha, J.K. Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis. Breast Cancer Res., 2020, 22(1), 11.
[] [PMID: 31992335]
Han, M.; Hu, J.; Lu, P.; Cao, H.; Yu, C.; Li, X.; Qian, X.; Yang, X.; Yang, Y.; Han, N.; Dou, D.; Zhang, F.; Ye, M.; Yang, C.; Gu, Y.; Dong, H. Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer. Cell Death Dis., 2020, 11(1), 43.
[] [PMID: 31969559]
Hessvik, N.P.; Llorente, A. Current knowledge on exosome biogenesis and release. Cell. Mol. Life Sci., 2018, 75(2), 193-208.
[] [PMID: 28733901]
Limoni, S.K.; Moghadam, M.F.; Moazzeni, S.M.; Gomari, H.; Salimi, F. Engineered exosomes for targeted transfer of siRNA to HER2 positive breast cancer cells. Appl. Biochem. Biotechnol., 2019, 187(1), 352-364.
[] [PMID: 29951961]
Wang, P.; Wang, H.; Huang, Q.; Peng, C.; Yao, L.; Chen, H.; Qiu, Z.; Wu, Y.; Wang, L.; Chen, W. Exosomes from M1-polarized macrophages enhance paclitaxel antitumor activity by activating macrophages-mediated inflammation. Theranostics, 2019, 9(6), 1714-1727.
[] [PMID: 31037133]
Salimi, F.; Forouzandeh Moghadam, M.; Rajabibazl, M. Development of a novel anti-HER2 scFv by ribosome display and in silico evaluation of its 3D structure and interaction with HER2, alone and after fusion to LAMP2B. Mol. Biol. Rep., 2018, 45(6), 2247-2256.
[] [PMID: 30225583]
Wang, J-H.; Forterre, A.V.; Zhao, J.; Frimannsson, D.O.; Delcayre, A.; Antes, T.J.; Efron, B.; Jeffrey, S.S.; Pegram, M.D.; Matin, A.C. Anti-HER2 scFv-directed extracellular vesicle-mediated mRNA-based gene delivery inhibits growth of HER2-positive human breast tumor xenografts by prodrug activation. Mol. Cancer Ther., 2018, 17(5), 1133-1142.
[] [PMID: 29483213]
Barok, M.; Puhka, M.; Vereb, G.; Szollosi, J.; Isola, J.; Joensuu, H. Cancer-derived exosomes from HER2-positive cancer cells carry trastuzumab-emtansine into cancer cells leading to growth inhibition and caspase activation. BMC Cancer, 2018, 18(1), 504.
[] [PMID: 29720111]
Yu, M.; Gai, C.; Li, Z.; Ding, D.; Zheng, J.; Zhang, W.; Lv, S.; Li, W. Targeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells. Cancer Sci., 2019, 110(10), 3173-3182.
[] [PMID: 31464035]
Gong, C.; Tian, J.; Wang, Z.; Gao, Y.; Wu, X.; Ding, X.; Qiang, L.; Li, G.; Han, Z.; Yuan, Y.; Gao, S. Functional exosome-mediated co-delivery of doxorubicin and hydrophobically modified microRNA 159 for triple-negative breast cancer therapy. J. Nanobiotechnology, 2019, 17(1), 93.
[] [PMID: 31481080]
Salvati, A.; Pitek, A.S.; Monopoli, M.P.; Prapainop, K.; Bombelli, F.B.; Hristov, D.R.; Kelly, P.M.; Åberg, C.; Mahon, E.; Dawson, K.A. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat. Nanotechnol., 2013, 8(2), 137-143.
[] [PMID: 23334168]
Sun, H.; Su, J.; Meng, Q.; Yin, Q.; Chen, L.; Gu, W.; Zhang, P.; Zhang, Z.; Yu, H.; Wang, S.; Li, Y. Cancer cell biomimetic nanoparticles for targeted therapy of homotypic tumors. Adv. Mater., 2016, 28(43), 9581-9588.
[] [PMID: 27628433]
Yong, T.; Zhang, X.; Bie, N.; Zhang, H.; Zhang, X.; Li, F.; Hakeem, A.; Hu, J.; Gan, L.; Santos, H.A.; Yang, X. Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy. Nat. Commun., 2019, 10(1), 3838.
[] [PMID: 31444335]
Pakravan, K.; Babashah, S.; Sadeghizadeh, M.; Mowla, S.J.; Mossahebi-Mohammadi, M.; Ataei, F.; Dana, N.; Javan, M. MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. Cell Oncol. (Dordr.), 2017, 40(5), 457-470.
[] [PMID: 28741069]
Lobos-González, L.; Bustos, R.; Campos, A.; Silva, V.; Silva, V.; Jeldes, E.; Salomon, C.; Varas-Godoy, M.; Cáceres-Verschae, A.; Duran, E.; Vera, T.; Ezquer, F.; Ezquer, M.; Burzio, V.A.; Villegas, J. Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells. Sci. Rep., 2020, 10(1), 343.
[] [PMID: 31941923]
Fu, W.; Lei, C.; Liu, S.; Cui, Y.; Wang, C.; Qian, K.; Li, T.; Shen, Y.; Fan, X.; Lin, F.; Ding, M.; Pan, M.; Ye, X.; Yang, Y.; Hu, S. CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity. Nat. Commun., 2019, 10(1), 4355.
[] [PMID: 31554797]
Shi, X.; Cheng, Q.; Hou, T.; Han, M.; Smbatyan, G.; Lang, J.E.; Epstein, A.L.; Lenz, H-J.; Zhang, Y. Genetically engineered cell-derived nanoparticles for targeted breast cancer immunotherapy. Mol. Ther., 2020, 28(2), 536-547.
[] [PMID: 31843452]
Molavipordanjani, S.; Khodashenas, S.; Abedi, S.M.; Moghadam, M.F.; Mardanshahi, A.; Hosseinimehr, S.J. 99mTc-radiolabeled HER2 targeted exosome for tumor imaging. Eur. J. Pharm. Sci., 2020, 148, 105312.
[] [PMID: 32198014]
Davidson, S.M.; Yellon, D.M. Exosomes and cardioprotection -a critical analysis. Mol. Aspects Med., 2018, 60, 104-114.
[] [PMID: 29122678]
Hirsch, A.M. Embryonic stem cell-derived exosomes increase the antiproliferative activity of doxorubicin in breast cancer. 2019.
Milano, G.; Biemmi, V.; Lazzarini, E.; Balbi, C.; Ciullo, A.; Bolis, S.; Ameri, P.; Di Silvestre, D.; Mauri, P.; Barile, L.; Vassalli, G. Intravenous administration of cardiac progenitor cell-derived exosomes protects against doxorubicin/trastuzumab-induced cardiac toxicity. Cardiovasc. Res., 2020, 116(2), 383-392.
[PMID: 31098627]
Stevic, I. Embryonic stem cell-derived exosomes increase the antiproliferative activity of doxorubicin in breast cancer. Virginia commonwealth university, VCU scholars compass; Theses and dissertations graduate school, 2019.
Donnarumma, E.; Fiore, D.; Nappa, M.; Roscigno, G.; Adamo, A.; Iaboni, M.; Russo, V.; Affinito, A.; Puoti, I.; Quintavalle, C.; Rienzo, A.; Piscuoglio, S.; Thomas, R.; Condorelli, G. Cancer-associated fibroblasts release exosomal microRNAs that dictate an aggressive phenotype in breast cancer. Oncotarget, 2017, 8(12), 19592-19608.
[] [PMID: 28121625]
Ni, Q.; Stevic, I.; Pan, C.; Müller, V.; Oliveira-Ferrer, L.; Pantel, K.; Schwarzenbach, H. Different signatures of miR-16, miR-30b and miR-93 in exosomes from breast cancer and DCIS patients. Sci. Rep., 2018, 8(1), 12974.
[] [PMID: 30154547]
Rodríguez-Martínez, A.; de Miguel-Pérez, D.; Ortega, F.G.; García-Puche, J.L.; Robles-Fernández, I.; Exposito, J.; Martorell- Marugan, J.; Carmona-Sáez, P.; Garrido-Navas, M.D.C.; Rolfo, C.; Ilyine, H.; Lorente, J.A.; Legueren, M.; Serrano, M.J. Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy. Breast Cancer Res., 2019, 21(1), 21.
[] [PMID: 30728048]
Ando, W.; Kikuchi, K.; Uematsu, T.; Yokomori, H.; Takaki, T.; Sogabe, M.; Kohgo, Y.; Otori, K.; Ishikawa, S.; Okazaki, I. Novel breast cancer screening: combined expression of miR-21 and MMP-1 in urinary exosomes detects 95% of breast cancer without metastasis. Sci. Rep., 2019, 9(1), 13595.
[] [PMID: 31537868]
Abdulhussain, M.M.; Hasan, N.A.; Hussain, A.G. Interrelation of the circulating and tissue microRNA-21 with tissue PDCD4 expression and the invasiveness of Iraqi female breast tumors. Indian J. Clin. Biochem., 2019, 34(1), 26-38.
[PMID: 30728670]
Xin, Y.; Wang, X.; Meng, K.; Ni, C.; Lv, Z.; Guan, D. Identification of exosomal miR-455-5p and miR-1255a as therapeutic targets for breast cancer. Biosci. Rep., 2020, 40(1), 40.
[] [PMID: 31763681]
Yoshikawa, M.; Iinuma, H.; Umemoto, Y.; Yanagisawa, T.; Matsumoto, A.; Jinno, H. Exosome-encapsulated microRNA-223-3p as a minimally invasive biomarker for the early detection of invasive breast cancer. Oncol. Lett., 2018, 15(6), 9584-9592.
[] [PMID: 29805680]
Hirschfeld, M.; Rücker, G.; Weiß, D.; Berner, K.; Ritter, A.; Jäger, M.; Erbes, T. Urinary exosomal MicroRNAs as potential non-invasive biomarkers in breast cancer detection. Mol. Diagn. Ther., 2020, 24(2), 215-232.
[] [PMID: 32112368]
Zhong, G.; Wang, K.; Li, J.; Xiao, S.; Wei, W.; Liu, J. Determination of serum exosomal H19 as a noninvasive biomarker for breast cancer diagnosis. OncoTargets Ther., 2020, 13, 2563-2571.
[] [PMID: 32273726]
Wang, Y-L.; Liu, L-C.; Hung, Y.; Chen, C-J.; Lin, Y-Z.; Wu, W-R.; Wang, S-C. Long non-coding RNA HOTAIR in circulatory exosomes is correlated with ErbB2/HER2 positivity in breast cancer. Breast, 2019, 46, 64-69.
[] [PMID: 31100572]
Chakrabortty, S.K.; Kitchen, R.R.; Coticchia, C.M.; Tadigotla, V.R.; Eitan, E.; Castellanos-Rizaldos, E.; Bedford, L.; Badola, S.; Valentino, M.D.; Colafemina, N. In: Abstract LB-226: Exosomal liquid biopsy reveals mRNA and lincRNA biomarkers in early stage breast cancer patient plasma; Proceeding: AACR Annual Meeting, Chicago, IL, April 14-18, 2018.
Yang, S.; Tang, J. Circular RNAs in exosomes derived from breast cancer: Promising biomarkers for diagnosis and prognosis of triple negative breast cancer (TNBC). J. Clin. Oncol., 2020, 38, 3528-3528.
Wang, X.; Zhong, W.; Bu, J.; Li, Y.; Li, R.; Nie, R.; Xiao, C.; Ma, K.; Huang, X.; Li, Y. Exosomal protein CD82 as a diagnostic biomarker for precision medicine for breast cancer. Mol. Carcinog., 2019, 58(5), 674-685.
[] [PMID: 30604894]
Cui, Z.; Chen, Y.; Hu, M.; Lin, Y.; Zhang, S.; Kong, L.; Chen, Y. Diagnostic and prognostic value of the cancer-testis antigen lactate dehydrogenase C4 in breast cancer. Clin. Chim. Acta, 2020, 503, 203-209.
[] [PMID: 31794764]
Li, R.; Chibbar, R.; Xiang, J. Novel EXO-T vaccine using polyclonal CD4+ T cells armed with HER2-specific exosomes for HER2- positive breast cancer. OncoTargets Ther., 2018, 11, 7089-7093.
[] [PMID: 30410365]
Xie, Y.; Wu, J.; Xu, A.; Ahmeqd, S.; Sami, A.; Chibbar, R.; Freywald, A.; Zheng, C.; Xiang, J. Heterologous human/rat HER2-specific exosome-targeted T cell vaccine stimulates potent humoral and CTL responses leading to enhanced circumvention of HER2 tolerance in double transgenic HLA-A2/HER2 mice. Vaccine, 2018, 36(11), 1414-1422.
[] [PMID: 29415817]
Anticoli, S.; Aricò, E.; Arenaccio, C.; Manfredi, F.; Chiozzini, C.; Olivetta, E.; Ferrantelli, F.; Lattanzi, L.; D’Urso, M.T.; Proietti, E.; Federico, M. Engineered exosomes emerging from muscle cells break immune tolerance to HER2 in transgenic mice and induce antigen-specific CTLs upon challenge by human dendritic cells. J. Mol. Med. (Berl.), 2018, 96(2), 211-221.
[] [PMID: 29282521]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy