The Mechanical Properties of Breast Cancer Cells and Their Surrounding Microenvironment - Research Review

Sep 23, 2026

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Breast cancer represents a major global health concern, making it essential to understand how breast cancer cells change during disease progression. Alterations in the mechanical properties of cancer cells—such as reduced adhesion forces and increased deformability in highly malignant cells—are closely tied to how cytoskeletal and extracellular matrix mechanics regulate behavior. Mechanical stresses can shape cancer-cell motility, proliferation, invasiveness, and microenvironment remodeling. The review analyzes mechanical characteristics of breast cancer cells and surrounding extracellular matrix, summarizes gene links to mechanical forces, and considers implications for diagnosis and treatment.

LanguageEnglish

CategoryHealthcare

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Pages13

Reading Time33 min

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Abstract

Breast Cancer Cells and Their Mechanical Properties

Cancer subtypes and stages

Mechanical properties linked to progression

Gap Junctions and Cell–Cell Communication

Connexins and adhesion forces

Population density effects

Tight Junctions, Membrane Viscoelasticity, and ECM Mechanics

Frequency shifts and dissipation measurements

Viscoelastic trends in metastatic vs non-invasive cells

Review The Mechanical Properties of Breast Cancer Cells and Their Surrounding Microenvironment Leila Jahangiri 1,2 Academic Editor: Davide Raineri Received: 23 April 2025 Revised: 24 May 2025 Accepted: 26 May 2025 Published: 28 May 2025 Citation: Jahangiri, L. The Mechanical Properties of Breast Cancer Cells and Their Surrounding Microenvironment. Int. J. Mol. Sci. 2025, 26, 5183. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms26115183](10.3390/ijms26115183) Copyright: © 2025 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 School of Science and Technology, Nottingham Trent University, Clifton Site, Nottingham NG11 8NS, UK; [leila.jahangiri@ntu.ac.uk](leila.jahangiri@ntu.ac.uk) 2 Division of Cellular and Molecular Pathology, Department of Pathology, Addenbrookes Hospital, University of Cambridge, Cambridge CB0 2QQ, UK Abstract: Breast cancer is a major health concern for women worldwide, and therefore, understanding various changes acquired by breast cancer cells is relevant to a better comprehension of the disease. One such change includes alterations to the mechanical properties of breast cancer cells. For example, cells with high malignant potential show lower adhesion forces and higher cell deformability. Mechanical forces, including tensile and compressive forces of the cytoskeleton and the extracellular matrix such as integrin, collagen, and the basement membrane, can affect BC cells. These forces alter the properties of cancer cells, drive them towards invasiveness due to different motility and proliferative profiles, and change their microenvironment. This study will focus on the mechanical characteristics of breast cancer cells and the extracellular matrix. Furthermore, changes induced in breast cancer cells following exposure to mechanical forces will be reviewed. Genes that link phenotype to mechanical forces and the implications of these forces for diagnostics and treatment will be discussed. Keywords: breast cancer; mechanical forces; extracellular matrix; invasion 1. Breast Cancer Cells and Their Mechanical Properties Breast cancer (BC) is a major health problem for women, and close to 13% of this group will be diagnosed with BC in their lifetime, while BC contributes to circa 25% of all cancers and 16% of cancer-related deaths in this group in the western world [1,2] . BC can be categorised based on immunohistochemical profiles and hormone receptor expression as oestrogen receptor-positive (ER+), progesterone receptor-positive (PR+), triple negative (TN−), and human epidermal growth factor receptor-positive (HER2+) . On these grounds, 4 distinct subtypes have been described, including luminal A and B, TN−, and HER2+ [3] . Accordingly, luminal A are usually ER+ and/or PR+, HER2−, and luminal B are usually ER+ and/or PR+, HER2+/ − . Further, the HER2+ category is ER−, PR−, and HER2+, and the TNBC subtype is negative for all three hormone receptors [4] . BC can be categorised into stages, akin to other cancers, which include in situ (0), signifying non-invasive BC. This is followed by early-stage invasion (IA, IB, IIA, and IIB) when limited invasion and lymph node involvement have been established. In addition, later stages are locally advanced (IIIA, IIIB, and IIIC), in which wider spreading in the chest and metastasis has occurred (IV) [5] . Furthermore, solid tumours such as BC will display altered mechanical properties compared to their normal tissue counterparts. These mechanical properties include stiffness, rigidity, adhesion, traction, and deformability (elasticity) . In addition, as the tumour progresses from its in situ state and carries out invasion and metastasis, the mechanical proper

FAQs

How do mechanical properties differ between non-invasive and metastatic breast cancer cells?

Non-invasive cells tend to be stiffer with viscous membranes and stiffer cytoskeletons, while metastatic cells are softer with lower viscous membrane character and soft cytoskeletons.

What mechanical factors influence breast cancer cell behavior?

Cytoskeletal and extracellular matrix forces, including tensile and compressive stresses mediated by components such as integrin, collagen, and the basement membrane, can alter cell properties and promote invasiveness.

How are cell–cell junctions involved in mechanical properties such as adhesion?

Gap junctions formed by connexin proteins support intracellular signaling exchange, and experimental assessment of connexin 43 (Cx43) shows adhesion forces increase in clustered Cx43-expressing cells, indicating effects of both Cx43 and population density on cell–cell adhesion.

Sep 23, 2026

Uploaded by Angel