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

被引：210

作者：

Friedman, Gil ^{[1
]}

Levi-Galibov, Oshrat ^{[1
]}

David, Eyal ^{[2
]}

Bornstein, Chamutal ^{[2
]}

Giladi, Amir ^{[2
]}

Dadiani, Maya ^{[3
]}

Mayo, Avi ^{[4
]}

Halperin, Coral ^{[1
]}

Pevsner-Fischer, Meirav ^{[1
]}

Lavon, Hagar ^{[1
]}

Mayer, Shimrit ^{[1
]}

Nevo, Reinat ^{[1
]}

Stein, Yaniv ^{[1
]}

Balint-Lahat, Nora ^{[5
]}

Barshack, Iris ^{[5
,6
]}

Ali, H. Raza ^{[7
]}

Caldas, Carlos ^{[7
,8
,9
]}

Nili-Gal-Yam, Einav ^{[10
]}

Alon, Uri ^{[4
]}

Amit, Ido ^{[2
]}

Scherz-Shouval, Ruth ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Biomol Sci, Rehovot, Israel

[2] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel

[3] Canc Res Ctr, Chaim Sheba Med Ctr, Tel Hashomer, Israel

[4] Weizmann Inst Sci, Dept Mol Cell Biol, Rehovot, Israel

[5] Pathol Inst, Tel Hashomer, Israel

[6] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel

[7] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England

[8] Univ Cambridge, Dept Oncol, Cambridge, England

[9] Canc Res UK Canc Ctr, Breast Canc Programme, Cambridge, England

[10] Chaim Sheba Med Ctr, Inst Oncol, Tel Hashomer, Israel

来源：

NATURE CANCER | 2020年 / 1卷 / 07期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

CLASS-II EXPRESSION; RNA-SEQ; CELLS; MYOFIBROBLASTS; HETEROGENEITY; SUPPRESSOR; CONTRIBUTE; EVOLUTION; NICHE;

D O I：

10.1038/s43018-020-0082-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Scherz-Shouval and colleagues characterize the dynamic changes in cancer-associated fibroblast subpopulations during breast cancer progression. They find that the ratio of S100A4(+) and PDPN+ CAF subsets is associated with clinical outcome.

引用

页码：692 / +

页数：29

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