Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4+ and PDPN+ CAFs to clinical outcome

Gil Friedman; Oshrat Levi-Galibov; Eyal David; Chamutal Bornstein; Amir Giladi; Maya Dadiani; Avi Mayo; Coral Halperin; Meirav Pevsner-Fischer; Hagar Lavon; Shimrit Mayer; Reinat Nevo; Yaniv Stein; Nora Balint-Lahat; Iris Barshack; H. Raza Ali; Carlos Caldas; Einav Nili-Gal-Yam; Uri Alon; Ido Amit; Ruth Scherz-Shouval

doi:10.1038/s43018-020-0082-y

Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4⁺ and PDPN⁺ CAFs to clinical outcome

Gil Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, Maya Dadiani, Avi Mayo, Coral Halperin, Meirav Pevsner-Fischer, Hagar Lavon, Shimrit Mayer, Reinat Nevo, Yaniv Stein, Nora Balint-Lahat, Iris Barshack, H. Raza Ali, Carlos Caldas, Einav Nili-Gal-Yam, Uri Alon, Ido Amit^*Ruth Scherz-Shouval^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

195 Scopus citations

Abstract

Tumors are supported by cancer-associated fibroblasts (CAFs). CAFs are heterogeneous and carry out distinct cancer-associated functions. Understanding the full repertoire of CAFs and their dynamic changes as tumors evolve could improve the precision of cancer treatment. Here we comprehensively analyze CAFs using index and transcriptional single-cell sorting at several time points along breast tumor progression in mice, uncovering distinct subpopulations. Notably, the transcriptional programs of these subpopulations change over time and in metastases, transitioning from an immunoregulatory program to wound-healing and antigen-presentation programs, indicating that CAFs and their functions are dynamic. Two main CAF subpopulations are also found in human breast tumors, where their ratio is associated with disease outcome across subtypes and is particularly correlated with BRCA mutations in triple-negative breast cancer. These findings indicate that the repertoire of CAF changes over time in breast cancer progression, with direct clinical implications.

Original language	English
Pages (from-to)	692-708
Number of pages	17
Journal	Nature Cancer
Volume	1
Issue number	7
DOIs	https://doi.org/10.1038/s43018-020-0082-y
State	Published - 1 Jul 2020

Funding

Funders	Funder number
Horizon 2020 Framework Programme	724471
Israel Science Foundation	1384/1, 401/17, 703/15
Cancer Research UK	C19767/A27145

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s43018-020-0082-y

Cite this

Friedman, G., Levi-Galibov, O., David, E., Bornstein, C., Giladi, A., Dadiani, M., Mayo, A., Halperin, C., Pevsner-Fischer, M., Lavon, H., Mayer, S., Nevo, R., Stein, Y., Balint-Lahat, N., Barshack, I., Ali, H. R., Caldas, C., Nili-Gal-Yam, E., Alon, U., ... Scherz-Shouval, R. (2020). Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4⁺ and PDPN⁺ CAFs to clinical outcome. Nature Cancer, 1(7), 692-708. https://doi.org/10.1038/s43018-020-0082-y

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abstract = "Tumors are supported by cancer-associated fibroblasts (CAFs). CAFs are heterogeneous and carry out distinct cancer-associated functions. Understanding the full repertoire of CAFs and their dynamic changes as tumors evolve could improve the precision of cancer treatment. Here we comprehensively analyze CAFs using index and transcriptional single-cell sorting at several time points along breast tumor progression in mice, uncovering distinct subpopulations. Notably, the transcriptional programs of these subpopulations change over time and in metastases, transitioning from an immunoregulatory program to wound-healing and antigen-presentation programs, indicating that CAFs and their functions are dynamic. Two main CAF subpopulations are also found in human breast tumors, where their ratio is associated with disease outcome across subtypes and is particularly correlated with BRCA mutations in triple-negative breast cancer. These findings indicate that the repertoire of CAF changes over time in breast cancer progression, with direct clinical implications.",

author = "Gil Friedman and Oshrat Levi-Galibov and Eyal David and Chamutal Bornstein and Amir Giladi and Maya Dadiani and Avi Mayo and Coral Halperin and Meirav Pevsner-Fischer and Hagar Lavon and Shimrit Mayer and Reinat Nevo and Yaniv Stein and Nora Balint-Lahat and Iris Barshack and Ali, {H. Raza} and Carlos Caldas and Einav Nili-Gal-Yam and Uri Alon and Ido Amit and Ruth Scherz-Shouval",

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Friedman, G, Levi-Galibov, O, David, E, Bornstein, C, Giladi, A, Dadiani, M, Mayo, A, Halperin, C, Pevsner-Fischer, M, Lavon, H, Mayer, S, Nevo, R, Stein, Y, Balint-Lahat, N, Barshack, I, Ali, HR, Caldas, C, Nili-Gal-Yam, E, Alon, U, Amit, I & Scherz-Shouval, R 2020, 'Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4⁺ and PDPN⁺ CAFs to clinical outcome', Nature Cancer, vol. 1, no. 7, pp. 692-708. https://doi.org/10.1038/s43018-020-0082-y

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