Cellular Plasticity in the Breast Cancer Ecosystem

Overview

Journal Ups J Med Sci

Specialty General Medicine

Date 2024 Apr 4

PMID 38571887

Authors

Kristian Pietras

Jonas Sjolund

Affiliations

Soon will be listed here.

Abstract

The complex interplay between genetically diverse tumor cells and their microenvironment significantly influences cancer progression and therapeutic responses. This review highlights recent findings on cellular plasticity and heterogeneity within the breast cancer ecosystem, focusing on the roles of cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). We discuss evidence suggesting that breast cancer cells exhibit phenotypic plasticity driven by both intrinsic genetic factors and external microenvironmental cues, impacting treatment responses and disease recurrence. Moreover, single-cell RNA sequencing studies reveal diverse subtypes of CAFs and TAMs, each with distinct functional gene expression programs and spatial organization within the tumor microenvironment. Understanding the hierarchical relationships and niche cues governing cellular phenotypes offers new opportunities for targeted therapeutic interventions. By elucidating the organizational principles of the tumor ecosystem, future therapies may target phenotypic states or entire cellular niches, advancing precision medicine approaches in breast cancer treatment.

Citing Articles

Role of the serum levels of the inter-organs messenger fibroblast growth factor 21 (FGF21) in the diagnosis and prognosis of breast cancer patients.

Ranuncolo S, Armanasco E, Nunez M, Yuan L, Makhkamov S, De Lorenzo M Cell Commun Signal. 2025; 23(1):37.

PMID: 39838482 PMC: 11753132. DOI: 10.1186/s12964-024-02003-z.

Special issue: frontiers in recent advances on cancer diagnosis and treatment.

Westermark B, Heldin C Ups J Med Sci. 2025; 129.

PMID: 39780954 PMC: 11708456. DOI: 10.48101/ujms.v129.11919.

References

Clara J, Monge C, Yang Y, Takebe N . Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update. Nat Rev Clin Oncol. 2019; 17(4):204-232. DOI: 10.1038/s41571-019-0293-2. View

Bartoschek M, Oskolkov N, Bocci M, Lovrot J, Larsson C, Sommarin M . Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing. Nat Commun. 2018; 9(1):5150. PMC: 6279758. DOI: 10.1038/s41467-018-07582-3. View

Roswall P, Bocci M, Bartoschek M, Li H, Kristiansen G, Jansson S . Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling. Nat Med. 2018; 24(4):463-473. PMC: 5896729. DOI: 10.1038/nm.4494. View

Azizi E, Carr A, Plitas G, Cornish A, Konopacki C, Prabhakaran S . Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment. Cell. 2018; 174(5):1293-1308.e36. PMC: 6348010. DOI: 10.1016/j.cell.2018.05.060. View

Ohlund D, Handly-Santana A, Biffi G, Elyada E, Almeida A, Ponz-Sarvise M . Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med. 2017; 214(3):579-596. PMC: 5339682. DOI: 10.1084/jem.20162024. View

Hanahan D, Coussens L . Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012; 21(3):309-22. DOI: 10.1016/j.ccr.2012.02.022. View

Lim E, Vaillant F, Wu D, Forrest N, Pal B, Hart A . Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med. 2009; 15(8):907-13. DOI: 10.1038/nm.2000. View

Su Y, Subedee A, Bloushtain-Qimron N, Savova V, Krzystanek M, Li L . Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer. Cell Rep. 2015; 11(10):1549-63. DOI: 10.1016/j.celrep.2015.05.011. View

Schubert M, Klinger B, Klunemann M, Sieber A, Uhlitz F, Sauer S . Perturbation-response genes reveal signaling footprints in cancer gene expression. Nat Commun. 2018; 9(1):20. PMC: 5750219. DOI: 10.1038/s41467-017-02391-6. View

10.

Wu S, Al-Eryani G, Roden D, Junankar S, Harvey K, Andersson A . A single-cell and spatially resolved atlas of human breast cancers. Nat Genet. 2021; 53(9):1334-1347. PMC: 9044823. DOI: 10.1038/s41588-021-00911-1. View

11.

Reid S, Pantaleo J, Bolivar P, Bocci M, Sjolund J, Morsing M . Cancer-associated fibroblasts rewire the estrogen receptor response in luminal breast cancer, enabling estrogen independence. Oncogene. 2024; 43(15):1113-1126. PMC: 10997519. DOI: 10.1038/s41388-024-02973-x. View

12.

Chiu-Tsun Tang P, Chung J, Xue V, Xiao J, Meng X, Huang X . Smad3 Promotes Cancer-Associated Fibroblasts Generation via Macrophage-Myofibroblast Transition. Adv Sci (Weinh). 2021; 9(1):e2101235. PMC: 8728853. DOI: 10.1002/advs.202101235. View

13.

Kieffer Y, Hocine H, Gentric G, Pelon F, Bernard C, Bourachot B . Single-Cell Analysis Reveals Fibroblast Clusters Linked to Immunotherapy Resistance in Cancer. Cancer Discov. 2020; 10(9):1330-1351. DOI: 10.1158/2159-8290.CD-19-1384. View

14.

Yamamoto S, Wu Z, Russnes H, Takagi S, Peluffo G, Vaske C . JARID1B is a luminal lineage-driving oncogene in breast cancer. Cancer Cell. 2014; 25(6):762-77. PMC: 4079039. DOI: 10.1016/j.ccr.2014.04.024. View

15.

Peyvandi S, Bulliard M, Yilmaz A, Kauzlaric A, Marcone R, Haerri L . Tumor-educated Gr1+CD11b+ cells drive breast cancer metastasis via OSM/IL-6/JAK-induced cancer cell plasticity. J Clin Invest. 2024; 134(6). PMC: 10940099. DOI: 10.1172/JCI166847. View

16.

Vulin M, Jehanno C, Sethi A, Correia A, Obradovic M, Couto J . A high-throughput drug screen reveals means to differentiate triple-negative breast cancer. Oncogene. 2022; 41(39):4459-4473. PMC: 9507968. DOI: 10.1038/s41388-022-02429-0. View

17.

Walsh L, Quail D . Decoding the tumor microenvironment with spatial technologies. Nat Immunol. 2023; 24(12):1982-1993. DOI: 10.1038/s41590-023-01678-9. View

18.

Lindstrom L, Karlsson E, Wilking U, Johansson U, Hartman J, Lidbrink E . Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol. 2012; 30(21):2601-8. DOI: 10.1200/JCO.2011.37.2482. View

19.

Bejarano L, Jordao M, Joyce J . Therapeutic Targeting of the Tumor Microenvironment. Cancer Discov. 2021; 11(4):933-959. DOI: 10.1158/2159-8290.CD-20-1808. View

20.

Batlle E, Clevers H . Cancer stem cells revisited. Nat Med. 2017; 23(10):1124-1134. DOI: 10.1038/nm.4409. View