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The combination of IDO and AHR blockers reduces the migration and clonogenicity of breast cancer cells

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Abstract

The indoleamine-2,3-dioxygenase (IDO) enzyme causes immunosuppressive consequences in the tumor microenvironment (TME). In addition, the role of aryl hydrocarbon receptor (AHR) in the TME is under discussion. The current study evaluated the role of the IDO and AHR blockers on cell migration, clonogenic, and IDO expression of murine breast cancer cells. The cell migration and clonogenic abilities of breast cancer cells are evaluated by wound‑healing assay (cell migration assay) and Colony formation assay (clonogenic assay). Also, flow cytometry analysis was used to detect the IDO-positive breast cancer cells. The results showed that treating cells with a combination of IDO and AHR blockers dramatically reduced breast cancer cells’ migration and clonogenic capacities. Treating cells with only AHR blockade suppressed the clonogenic rate. Since both IDO and AHR are involved in their complex molecular networks, blocking both IDO and AHR might cause alterations in their molecular networks resulting in diminishing the migration and clonogenic abilities of breast cancer cells. However, further investigations are required to confirm our findings within in vivo models as a novel therapy for breast cancer.

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Abbreviations

IDO:

Indoleamine-2,3-dioxygenase

TME:

Tumor microenvironment

AHR:

Aryl hydrocarbon receptor

Trp:

Tryptophan

IGF:

Insulin-like growth factor

1MT:

1-Methyl-DL-tryptophan

FBS:

Fetal bovine serum

STAT6:

Signal transducer and activator of transcription 6

NF-κB:

Nuclear factor kappa B

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Acknowledgements

The authors would like to thank BioRender.com for its services. Figure 4 was created with Biorender.com. This work was funded by FAPESP (2022/16332-1 to Jose Roberto Kfoury Junior). Also, the author thanks the National Council for the Improvement of Higher Education (CAPES) and the National Council for Scientific and Technological Development (CNPq) for the support of the scholarship.

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Author notes

  1. Maryam Soltani-asl and Parviz Azimnasab-sorkhabi contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, School of Veterinary Medicine and Animal Sciences, University of Sao Paulo, Sao Paulo, Brazil

    Maryam Soltani-asl, Parviz Azimnasab-sorkhabi, Tulio Teruo Yoshinaga & Jose Roberto Kfoury Jr.

  2. Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of Sao Paulo, Sao Paulo, Brazil

    Cristina de Oliveira Massoco

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  1. Maryam Soltani-asl
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Contributions

The original idea was designed by Maryam Soltaniasl, Parviz azimnasab-sorkhabi, and Jose Roberto Kfoury Junior. Material preparation, data collection, and analysis were performed by Maryam Soltaniasl and Parviz azimnasab-sorkhabi. The original draft was written by Maryam Soltani-asl, Parviz azimnasab-sorkhabi, and Túlio Teruo Yoshinaga. Critical review was performed by Maryam Soltani-asl, Parviz azimnasab-sorkhabi, Cristina de Oliveira Massoco, and Jose Roberto Kfoury Junior.

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Correspondence to Maryam Soltani-asl.

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Soltani-asl, M., Azimnasab-sorkhabi, P., Yoshinaga, T.T. et al. The combination of IDO and AHR blockers reduces the migration and clonogenicity of breast cancer cells. Immunol Res (2023). https://doi.org/10.1007/s12026-023-09450-9

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