Cancer-associated Fibroblast Compositions Change with Breast Cancer Progression Linking the Ratio of S100A4 and PDPN CAFs to Clinical Outcome

Overview

Journal Nat Cancer

Specialty Oncology

Date 2022 Feb 5

PMID 35122040

Authors

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

Affiliations

Soon will be listed here.

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.

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