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Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model

View ORCID ProfileOle Vidhammer Bjørnstad, View ORCID ProfileManuel Carrasco, View ORCID ProfileKenneth Finne, View ORCID ProfileIngeborg Winge, Cecilie Askeland, Jarle B. Arnes, Gøril Knutsvik, View ORCID ProfileDimitrios Kleftogiannis, Joao A. Paulo, View ORCID ProfileLars A. Akslen, View ORCID ProfileHeidrun Vethe
doi: https://doi.org/10.1101/2023.05.03.539050
Ole Vidhammer Bjørnstad
1Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, N-5021, Norway
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Manuel Carrasco
1Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, N-5021, Norway
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Kenneth Finne
1Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, N-5021, Norway
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Ingeborg Winge
1Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, N-5021, Norway
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Cecilie Askeland
2Department of Pathology, Haukeland University Hospital, Bergen, N-5021, Norway
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Jarle B. Arnes
2Department of Pathology, Haukeland University Hospital, Bergen, N-5021, Norway
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Gøril Knutsvik
2Department of Pathology, Haukeland University Hospital, Bergen, N-5021, Norway
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Dimitrios Kleftogiannis
1Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, N-5021, Norway
3Computational Biology Unit (CBU), Department of Informatics, University of Bergen, Bergen, N-5021, Norway
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Joao A. Paulo
3Computational Biology Unit (CBU), Department of Informatics, University of Bergen, Bergen, N-5021, Norway
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Lars A. Akslen
1Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, N-5021, Norway
2Department of Pathology, Haukeland University Hospital, Bergen, N-5021, Norway
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Heidrun Vethe
1Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, N-5021, Norway
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  • For correspondence: heidrun.vethe@uib.no
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Abstract

Tumor neurogenesis, a process by which new nerves invade tumors, is a growing area of interest in cancer research. Nerve presence has been linked to aggressive features of various solid tumors, including breast and prostate cancer. A recent study suggested that the tumor microenvironment may influence cancer progression through recruitment of neural progenitor cells from the central nervous system. However, the presence of neural progenitors in human breast tumors has not been reported. Here, we investigate the presence of Doublecortin (DCX) and Neurofilament-Light (NFL) co-expressing (DCX+/NFL+) cells in patient breast cancer tissue using Imaging Mass Cytometry. To map the interaction between breast cancer cells and neural progenitor cells further, we created an in vitro model mimicking breast cancer innervation, and characterized using mass spectrometry-based proteomics on the two cell types as they co- evolved in co-culture. Our results indicate stromal presence of DCX+/NFL+ cells in breast tumor tissue from a cohort of 107 patient cases, and that neural interaction contribute to drive a more aggressive breast cancer phenotype in our co-culture models. Our results support that neural involvement plays an active role in breast cancer and warrants further studies on the interaction between nervous system and breast cancer progression.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD040662

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model
Ole Vidhammer Bjørnstad, Manuel Carrasco, Kenneth Finne, Ingeborg Winge, Cecilie Askeland, Jarle B. Arnes, Gøril Knutsvik, Dimitrios Kleftogiannis, Joao A. Paulo, Lars A. Akslen, Heidrun Vethe
bioRxiv 2023.05.03.539050; doi: https://doi.org/10.1101/2023.05.03.539050
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Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model
Ole Vidhammer Bjørnstad, Manuel Carrasco, Kenneth Finne, Ingeborg Winge, Cecilie Askeland, Jarle B. Arnes, Gøril Knutsvik, Dimitrios Kleftogiannis, Joao A. Paulo, Lars A. Akslen, Heidrun Vethe
bioRxiv 2023.05.03.539050; doi: https://doi.org/10.1101/2023.05.03.539050

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