Tocilizumab potentiates cisplatin cytotoxicity and targets cancer stem cells in triple-negative breast cancer

Molecular Carcinogenesis
Noura N AlraoujiAbdelilah Aboussekhra

Abstract

Triple-negative breast cancer (TNBC) is a very aggressive subtype with high recurrence rate and no molecular targets for therapies. This subtype is characterized by high expression/secretion of the proinvasive/metastatic interleukin-6 (IL-6) cytokine. In the present study, we have shown that tocilizumab inhibits the IL-6/STAT3 signaling and suppresses the cancer/inflammatory epigenetic IL-6/STAT3/NF-κB positive feedback loop. Furthermore, tocilizumab inhibited the proliferative and the migratory/invasiveness capacities as well as the epithelial-to-mesenchymal transition (EMT) process in TNBC cells. Importantly, tocilizumab suppressed the stemness-related characteristics of TNBC cells, through the inhibition of the Wnt/β-catenin breast cancer stem cell-related pathway. Additionally, we have shown that tocilizumab suppresses the paracrine activation of normal breast stromal fibroblasts to myofibroblats. Moreover, tocilizumab sensitized TNBC cells to the cytotoxic effect of cisplatin in vitro. Furthermore, pharmacological inhibition of IL-6 by tocilizumab had great inhibitory effect on tumor growth and the EMT process in humanized orthotopic breast tumors in mice. In addition, tocilizumab potentiated the proapoptotic effect of cis...Continue Reading

References

Oct 3, 2003·Cell Proliferation·Gabriela DontuMax S Wicha
Dec 13, 2006·Nucleic Acids Research·Mai A Al-MohannaAbdelilah Aboussekhra
Jan 22, 2008·Nature Cell Biology·Jer-Yen YangMien-Chie Hung
Apr 17, 2008·Cancer Research·Nahed M HawsawiAbdelilah Aboussekhra
Aug 27, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Satoru ShinrikiYukio Ando
Jan 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dimitrios IliopoulosKevin Struhl
Feb 8, 2011·World Journal of Surgical Oncology·Praveen Ravishankaran, R Karunanithi
Jul 3, 2013·Neoplasia : an International Journal for Oncology Research·Qing ChangJacqueline Bromberg
Apr 17, 2015·World Journal of Surgical Oncology·Alessandro SanguinettiNicola Avenia
Jul 29, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E M DijkgraafJ R Kroep
Aug 20, 2015·Oncotarget·Daiki MochizukiJacques E Nör
Dec 30, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fengting LiuSamir G Agrawal
Sep 13, 2016·Oncogene·T ZhanM Boutros
Feb 7, 2018·Nature Reviews. Clinical Oncology·Daniel E JohnsonJennifer R Grandis

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Citations

Dec 3, 2020·Molecular Carcinogenesis·Noura N Alraouji, Abdelilah Aboussekhra
Nov 19, 2020·International Journal of Molecular Sciences·Alisson ClemenceauFrancine Durocher
Feb 23, 2021·Toxicology Research·Aref NazariMehdi Aliomrani
Jun 3, 2021·Molecular Neurobiology·Don A DaviesBenedict C Albensi
Jul 9, 2021·Frontiers in Cell and Developmental Biology·Martina Mang Leng Lei, Terence Kin Wah Lee
Jan 16, 2022·Clinical Reviews in Allergy & Immunology·Augusto BleveAntonio Sica

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