Cancer‐associated fibroblasts in breast cancer: Challenges and opportunities

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Abstract

The tumor microenvironment is proposed to contribute substantially to the progression of cancers, including breast cancer. Cancer‐associated fibroblasts (CAFs) are the most abundant components of the tumor microenvironment. Studies have revealed that CAFs in breast cancer originate from several types of cells and promote breast cancer malignancy by secreting factors, generating exosomes, releasing nutrients, reshaping the extracellular matrix, and suppressing the function of immune cells. CAFs are also becoming therapeutic targets for breast cancer due to their specific distribution in tumors and their unique biomarkers. Agents interrupting the effect of CAFs on surrounding cells have been developed and applied in clinical trials. Here, we reviewed studies examining the heterogeneity of CAFs in breast cancer and expression patterns of CAF markers in different subtypes of breast cancer. We hope that summarizing CAF‐related studies from a historical perspective will help to accelerate the development of CAF‐targeted therapeutic strategies for breast cancer.

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Most cited references 364

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

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A framework for advancing our understanding of cancer-associated fibroblasts

Erik Sahai, Igor Astsaturov, Edna Cukierman … (2020)

Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.

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The biology and function of fibroblasts in cancer.

Raghu Kalluri (2016)

Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying tissue. Their resilient adaptation may reside in their intrinsic survival programmes and cellular plasticity. Cancer is associated with fibroblasts at all stages of disease progression, including metastasis, and they are a considerable component of the general host response to tissue damage caused by cancer cells. Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components. CAFs have a role in creating extracellular matrix (ECM) structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy. The pleiotropic actions of CAFs on tumour cells are probably reflective of them being a heterogeneous and plastic population with context-dependent influence on cancer.

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Author and article information

Contributors

Jichun Zhou: jichun-zhou@zju.edu.cn

Linbo Wang:

ORCID: https://orcid.org/0000-0003-0526-1990

linbowang@zju.edu.cn

Journal

Journal ID (nlm-ta): Cancer Commun (Lond)

Journal ID (iso-abbrev): Cancer Commun (Lond)

Journal ID (doi): 10.1002/(ISSN)2523-3548

Journal ID (publisher-id): CAC2

Title: Cancer Communications

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2523-3548

Publication date (Electronic): 28 April 2022

Publication date Collection: May 2022

Volume: 42

Issue: 5 ( doiID: 10.1002/cac2.v42.5 )

Pages: 401-434

Affiliations

[ ¹ ] Affiliated Cixi Hospital Wenzhou Medical University Ningbo Zhejiang 315300 P. R. China

[ ² ] Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education) Hangzhou Zhejiang 310016 P. R. China

[ ³ ] Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province Hangzhou Zhejiang 310016 P. R. China

Author notes

[*] [* ] Correspondence

Linbo Wang, Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, No.3 Eastern Qingchun Road, Hangzhou, Zhejiang, 310016, P. R. China.

Email: linbowang@ 123456zju.edu.cn

Jichun Zhou, Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, No.3 Eastern Qingchun Road, Hangzhou, Zhejiang, 310016, P. R. China. Email: jichun-zhou@ 123456zju.edu.cn

[†]

These authors contributed equally to this work.

Author information

Linbo Wang https://orcid.org/0000-0003-0526-1990

Article

Publisher ID: CAC212291

DOI: 10.1002/cac2.12291

PMC ID: 9118050

PubMed ID: 35481621

SO-VID: cd1194ad-76a6-4b0c-ba74-204f544456ae

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

History

Date revision received : 06 February 2022

Date received : 11 November 2021

Date accepted : 07 April 2022

Page count

Figures: 5, Tables: 3, Pages: 34, Words: 23219

Funding

Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;

Award ID: 81602471

Award ID: 81672729

Award ID: 81972453

Award ID: 81972597

Funded by: Natural Science Foundation of Zhejiang Province , doi 10.13039/501100004731;

Award ID: LY19H160055

Award ID: LY19H160059

Award ID: LR22H160011

Funded by: Natural Science Foundation of Ningbo , doi 10.13039/100007834;

Award ID: 2019A610315

Funded by: Cixi Agricultural and Social Development Science and Technology Project

Award ID: CN2020006

Funded by: Zheng Shu Medical Elite Scholarship Fund

Custom metadata

source-schema-version-number 2.0

cover-date May 2022

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.6 mode:remove_FC converted:19.05.2022

Keywords: cancer‐associated fibroblasts,breast cancer,therapeutic target,tumor microenvironment,biomarker,tumor heterogeneity

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Keywords: cancer‐associated fibroblasts, breast cancer, therapeutic target, tumor microenvironment, biomarker, tumor heterogeneity

Cancer‐associated fibroblasts in breast cancer: Challenges and opportunities

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Karger: Oncology

Most cited references 364

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

A framework for advancing our understanding of cancer-associated fibroblasts

The biology and function of fibroblasts in cancer.

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