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ORIGINAL RESEARCH ARTICLE

Role of the IL-8/CXCR2 axis in promoting vasculogenic mimicry in triple-negative breast cancer through epithelial-mesenchymal transition

Saheed Abdulkarim1 ,  Jude Tetteh Quarshie1 ,  Peggy Afua Birokorang1 ,  Mawusi Adepa Mawuli2 ,  Samuel Mensah Baffoe1 ,  Afua Owusua Darkwah Abrahams2 ,  Anastasia Rosebud Aikins1*
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1 West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry Cell and Molecular Biology, University of Ghana, Accra, Greater Accra Region, Ghana
2 Department of Pathology, School of Medicine and Dentistry, University of Ghana Medical School, Accra, Greater Accra Region, Ghana
CP 2024, 6(2), 3356
Submitted: 4 April 2024 | Accepted: 20 June 2024 | Published: 2 July 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Vasculogenic mimicry (VM) — a phenomenon where tumor cells form de novo vascular networks independent of endothelial cells — supports the growth of highly aggressive tumors, including triple-negative breast cancer (TNBC). Evidence indicates that the interleukin 8 (IL-8)/CXCR2 axis and epithelial-mesenchymal transition (EMT) independently promote VM in TNBC. This study tested the hypothesis that the IL-8/CXCR2 axis promotes VM via EMT. Tissue samples from 71 female breast cancer cases (age range: 50 – 55 years), comprising 37 TNBC and 34 non-TNBC cases, were retrieved from the Department of Pathology at the University of Ghana Medical School. Out of the 37 TNBC tissues, 10 expressed either IL-8, CXCR2, or vimentin exclusively; three expressed all three markers; and 14 did not express any of these markers. For the non-TNBC tissues, 31 expressed CXCR2 (alone or co-expression with IL-8 and/or vimentin), 27 co-expressed IL-8 with CXCR2 and/or vimentin, and two expressed all three markers. Notably, 24 of the 37 non-TNBC tissues co-expressed IL-8 and CXCR2. A phi coefficient analysis displayed an inverse relationship between CXCR2 or IL-8 expression and TNBC and a positive correlation between vimentin expression and TNBC. Inhibiting the IL-8/CXCR2 axis with the CXCR2 antagonist SB225002 suppressed VM in MDA-MB-231 breast cancer cells. In addition, inhibiting the IL-8/CXCR2 axis using SB225002 and siRNA-mediated CXCR2 knockdown suppressed EMT by upregulating E-cadherin expression and downregulating N-cadherin and vimentin expression. Our findings suggest that the IL-8/CXCR2 signaling axis promotes VM in TNBC by facilitating EMT. Therefore, therapies targeting IL-8/CXCR2 may be used to suppress EMT and VM in TNBC simultaneously.

Keywords
Epithelial-mesenchymal transition
Interleukin-8
CXC chemokine receptor 2
Triple-negative breast cancer
Vasculogenic mimicry
Funding
Saheed Abdulkarim was supported by a DELTAS Africa grant (DEL-15-007: Awandare). This research was funded in whole, or in part, by the Wellcome Trust (DEL-15-007) and the UK Foreign, Commonwealth & Development Office, with support from the Developing Excellence in Leadership, Training, and Science in Africa (DELTAS Africa) program.
Conflict of interest
The authors declare that they have no competing interests.
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