The Mechanical Properties of Breast Cancer Cells and Their Surrounding Microenvironment
Abstract
1. Breast Cancer Cells and Their Mechanical Properties
2. The Mechanical Properties of the ECM and the Cytoskeleton
2.1. Integrin and Collagen
2.2. Basement Membrane
2.3. Fibroblasts and the ECM
3. Changes Induced in BC Cells Following Exposure to Forces
3.1. Forces Inducing Epithelial-to-Mesenchymal Transition (EMT), Dormancy, and Stemness
3.2. Changes Induced by Passing Through Narrow Pores
4. Genes Linking BC Phenotype and Mechanical Forces, and the Implications for Treatment
5. Conclusions
- Non-invasive BC cells showed viscous membranes but stiffer cells, while metastatic cells showed lower viscous membranes but softer cells. The higher the cell’s malignant potential, the lower the adhesion and the higher the cell deformability [8]. For example, MCF-7 demonstrated greater adhesion and intracellular forces, and stiff phenotypes compared to invasive cells [10,11,12,13]. Overall, this study shed light on the mechanical properties of the BC cells.
- The ECM also played a role in force dynamics. In the presence of HA, β1-integrin and CD44 were required for traction force generation [15]. This was important since the interplay between transmembrane proteins, GAGs and mechanical forces can inform future studies. Integrin-related mechanical tensions and BC cells during migration were also significant [16]. Collagen pore size and number increase influenced the mechanical properties of MDA-MB-231 cells by reducing the forces exerted by the cells on the ECM [17]. This finding applies to the composition of various hydrogels and scaffoldings used in BC studies. A stronger invasion capacity was obtained for a higher elastic modulus for thick fibril networks [18]. This directly impacted invasive phenotypes and therefore is significant. BC cells also used force and proteases to invade the basement membrane, as shown by others [19,44]. If the cancer cell was in contact with the ECM rather than a fibroblast, it experienced higher stress levels. In addition, TGFβ-activated fibroblasts could form a ring around the BC cells, modulating their movement [20,21]. Both aspects can be considered when designing systems to emulate the BC tumour microenvironment.
- Changes in BC cells following force exposure were discussed. HER2+ BC xenograft tumours in stiffened collagen gels expressed markers of EMT and β1 integrin [22]. This indicates a direct link between stiffened matrices and increased cell motility. The MCF-7 cells grown in higher Pascal force matrices became dormant. As such, the greater the stiffness of the gel, the greater the G0/G1 arrest and the potential for dormancy [24,25]. These aspects were particularly interesting when considering in vivo changes that induce dormancy following “mechanosensing” [45]. BC cells in stiff matrices showed high NANOG and TAZ levels and stemness [26]. In other words, the niche stiffness could impact cancer stemness in BC cells, and this was orchestrated by a host of key stemness transcriptional regulators. On a side note, changes to BC cells following transit through narrow capillaries were discussed. As a result, nuclear rupture of BC cells occurred. These constriction forces triggered inflammatory pathways and changed proliferation and nuclear stiffness. Cells also became more deformable [27,43].
- Genes linked BC phenotypes with mechanical forces. Inhibiting the interaction between Par3 and aPKC increased BC cell migration. Inhibiting NF-κB suppressed DSC1 levels and proliferation and affected cell stiffness [28,29]. This suggested gene expression, the cytoskeleton, and important BC cell activities, including migration and proliferation, were linked to the mechanical properties of BC cells. Finally, implications for diagnostics and treatment were assessed. Image processing and intricate algorithms could be diagnostic tools to detect cells with unusually high metabolic needs [30]. Also, vinculin and FAK activity could be BC treatment resistance indicators. The implications of cell–ECM junction tightness and high vinculin were limited migration post-treatment [31,32]. The dual role of vinculin in these two scenarios indicates the complexity of its function in the cell. Mechanical methods can suppress metastasis and alter the disease progression route [33,34]. Overall, understanding the mechanics of BC cells and the ECM will improve treatment.
Funding
Conflicts of Interest
Abbreviations
Cx43 | connexin 43 |
DSC1 | desmocolin-1 |
ECM | extracellular matrix |
EMT | epithelial-to-mesenchymal transition |
ER+ | oestrogen receptor-positive |
FAK | focal adhesion kinase |
GAG | glycosaminoglycan |
HA | hyaluronic acid |
HER2+ | human epidermal growth factor receptor-positive |
IGFBP5 | insulin growth factor binding receptor 5 |
IPN | Interpenetrating network |
nN | Nanonewton |
NLS | nuclear localisation signal |
NOD/SCID | non-obese diabetic/severe combined immunodeficiency |
PR+ | progesterone receptor-positive |
QPI | quantitative phase imaging |
TGT | tension gauge tethering |
TN− | triple-negative |
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Players | Mechanism | References |
---|---|---|
Non-invasive and metastatic BC cells | Non-invasive cells had viscous membranes but were stiff, and metastatic cells had less viscous membranes but were soft. | [8,9] |
MCF-10A compared to MCF-7 and MDA-MB-231 cells | Highest Young’s modulus (stiffness) in non-malignant cells. | [11] |
HA, traction force, β1-integrin in HA gels, and CD44 | Blocking CD44 or β1-integrin using antibodies in H2 conditions (collagen I and higher HA gels) reduced traction forces. | [15] |
Integrin, adhesion, and EGF | With EGF, cells became more polarised, and it affected integrin-mediated adhesion and cell migration. | [16] |
Collagen properties in hydrogels | Collagen pore size and number affected the mechanical properties of MDA-MB-231 cells by reducing the forces these cells exerted on the ECM. | [17] |
MDA-MB-231 cells and aggressiveness | The higher elastic modulus for thick fibril networks induced a stronger invasion capacity in MDA-MB-231 cells. | [18] |
Basement membrane breach, FAK, forces, and proteases | Basement membrane openings had high FAK activity; BC cells used force and proteases to stretch and invade the basement membrane. | [19] |
Softer and stiffer ECMs, BC cells, and invasion | In tissues with softer ECMs, cancer cells experienced high stress compared to stiffer ECMs. | [20] |
Coculture of fibroblasts with BC cells (COAFs) | Vinculin and inner negative traction forces were localised to activated fibroblasts, while COAFs had low migratory capacity. | [21] |
Stiff ECMs, invasion, and EMT | Stiff ECMs promoted growth, invasiveness, and EMT. These tumours increased β1 integrin, YAP, FAKY397, vimentin, SNAI2, and TWIST. | [22,23] |
Matrices with 450 and 1050 Pascal forces or 90 Pascal forces | 450 and 1050 Pascal groups showed low proliferation, and 90 Pascal groups showed high proliferation. | [24] |
3D Matrigel with 450 Pascal (high stiffness) | The greater the stiffness of the gel, the higher the G0/G1 arrest; 3D Matrigel with 450 Pascal forces drove cell cycle arrest and quiescence. | [25] |
Stiff matrices and BC cells | The abundance of ALDH1+CK+ (stem cells) was greater in stiff matrices. | [26] |
Constriction forces, proliferation, and BC cells | Constriction forces increased proliferation and Lamin A/C reorganisation in MCF-10A cells more than in BC cells. | [27] |
Par3, the cytoskeleton, and invasion | The Par3-siRNA-mediated knockdown in MDA-MB-231 cells reduced cytoskeletal stability and induced cancer invasion. | [28] |
NF-κB inhibitor (parthenolide) and DSC1 | Parthenolide decreased DSC1 levels in BC cells. DSC1 expression reduced cell height, and parthenolide decreased stiffness in these cells. | [29] |
MDA-MB-231 metastatic cells and metabolism | MDA-MB-231 metastatic cells showed a greater increase in dry mass fluctuations and areas of high metabolic activity. | [30] |
MDA-MB-231 cells, MCF-7 resistant cells, and MCF-7 cells | Actin stress fibres and vinculin were high in MDA-MB-231- and MCF-7-resistant cells compared to MCF-7 cells. | [31] |
Post-treatment BC cells | In post-treatment BC cells, large adhesion forces were needed to separate cells from the ECM, migration was low, and vinculin was high. | [32] |
Gradient RMF and magnetic photothermal converter | Gradient RMF affected the CCDC150 gene in BC cells and suppressed migration. TNBC was treated with a magnetic photothermal converter. | [33,34] |
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Jahangiri, L. The Mechanical Properties of Breast Cancer Cells and Their Surrounding Microenvironment. Int. J. Mol. Sci. 2025, 26, 5183. https://doi.org/10.3390/ijms26115183
Jahangiri L. The Mechanical Properties of Breast Cancer Cells and Their Surrounding Microenvironment. International Journal of Molecular Sciences. 2025; 26(11):5183. https://doi.org/10.3390/ijms26115183
Chicago/Turabian StyleJahangiri, Leila. 2025. "The Mechanical Properties of Breast Cancer Cells and Their Surrounding Microenvironment" International Journal of Molecular Sciences 26, no. 11: 5183. https://doi.org/10.3390/ijms26115183
APA StyleJahangiri, L. (2025). The Mechanical Properties of Breast Cancer Cells and Their Surrounding Microenvironment. International Journal of Molecular Sciences, 26(11), 5183. https://doi.org/10.3390/ijms26115183