Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

CXCL1/CXCR2 and CCL5/CCR1/CCR5 Promote Radiation-Induced Reprogramming of Breast Non-cancer Stem Cells into Cancer Stem Cells and Predict Patient Clinical Outcome

Justine Bailleul
ORCID logo ,
Mathilde Brulé
,
Nadège Bidan
,
Marie Denoulet
,
Raphaelle Mouttet Audouard
,
Sophie Cousin
,
Emmanuel Bouchaert
,
Jerome Benoit
,
Robert-Alain Toillon
ORCID logo ,
Pascal Finetti
ORCID logo ,
Daniel Birnbaum
,
François Bertucci
ORCID logo ,
Eric Adriaenssens
,
Xuefen Le Bourhis
ORCID logo ,
Chann Lagadec
* ORCID logo
Version 1 : Received: 6 February 2024 / Approved: 7 February 2024 / Online: 7 February 2024 (06:27:18 CET)

How to cite: Bailleul, J.; Brulé, M.; Bidan, N.; Denoulet, M.; Mouttet Audouard, R.; Cousin, S.; Bouchaert, E.; Benoit, J.; Toillon, R.; Finetti, P.; Birnbaum, D.; Bertucci, F.; Adriaenssens, E.; Le Bourhis, X.; Lagadec, C. CXCL1/CXCR2 and CCL5/CCR1/CCR5 Promote Radiation-Induced Reprogramming of Breast Non-cancer Stem Cells into Cancer Stem Cells and Predict Patient Clinical Outcome. Preprints 2024, 2024020403. https://doi.org/10.20944/preprints202402.0403.v1 Bailleul, J.; Brulé, M.; Bidan, N.; Denoulet, M.; Mouttet Audouard, R.; Cousin, S.; Bouchaert, E.; Benoit, J.; Toillon, R.; Finetti, P.; Birnbaum, D.; Bertucci, F.; Adriaenssens, E.; Le Bourhis, X.; Lagadec, C. CXCL1/CXCR2 and CCL5/CCR1/CCR5 Promote Radiation-Induced Reprogramming of Breast Non-cancer Stem Cells into Cancer Stem Cells and Predict Patient Clinical Outcome. Preprints 2024, 2024020403. https://doi.org/10.20944/preprints202402.0403.v1

Abstract

Cancer stem cell (CSC) has paved the way to many fundamental and translational studies. Recent studies have highlighted differentiated breast cancer cells (non-CSCs) switching phenotype to CSCs in response to various stimuli, depicting the existence of cancer stem cell plasticity. Although strategies to reduce the phenotypic plasticity of non-CSCs into CSCs are likely to prevent treatment-resilient cancer cells driving recurrence, most phenotypic plasticity mechanisms involve Notch, Wnt or MAPK signaling pathways. In this study, breast cancer cells were irradiated to identify soluble reprogramming factors. Using conditioned medias, protein arrays analyses, flow cytometry and in cellulo/in vivo functional assays, we demonstrated, for the first time, that radiation-induced chemokine expression, especially CXCL1 and CCL5 and their receptors CXCR2, CCR1 and CCR5, stimulates reprogramming of breast non-CSCs into CSCs. Treatment of non-CSCs with recombinant CXCL1 and CCL5 is sufficient to induce cell reprogramming, while their inhibition can be used to prevent reprogramming and sensitize tumor to radiation. Moreover, analysis of gene expression profiles from 38 public merged databases demonstrated that combined over-expression of CXCL1/CXCR2, CCL5/CCR1 or CCL5/CCR5 has a poorer prognosis in patients treated with radiotherapy, suggesting a promising way for patient stratification, where individuals with elevated cytokine levels could benefit from radiotherapy in conjunction with cytokine inhibitors. Taken together, our findings provide a rationale to consider these axes as potential targets and predictive biomarkers in breast cancer patients.

Keywords

Cancer Stem Cells; Breast Cancer; Reprogramming; Chemokines; Radiotherapy

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.