The effect of substrate stiffness on cancer cell volume homeostasis

• Published in: Journal of cellular physiology 2018-02, Vol.233 (2), p.1414-1423
• Main Authors: Wang, Meng, Chai, Na, Sha, Baoyong, Guo, Manyun, Zhuang, Jian, Xu, Feng, Li, Fei
• Format: Article
• Language: English
• Subjects: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology; Acrylic Resins - chemistry; Anion Transport Proteins - antagonists & inhibitors; Anion Transport Proteins - metabolism; Anions; Antineoplastic Agents, Hormonal - pharmacology; Benzazepines - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cell Adhesion; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Membrane - pathology; Cell Membrane Permeability; Cell migration; Cell Movement; Cell size; Cell Size - drug effects; cell volume; cellular mechanical microenvironment; Collagen - metabolism; Dopamine; Erythrocytes; Female; Homeostasis; Humans; Hydrogels; Hypotonic Solutions - pharmacology; Ion channels; MCF-7 Cells; MCF‐7 cell; Membrane permeability; Metastases; Osmoregulation - drug effects; Osmosis; Permeability; Porosity; Receptors, Dopamine D1 - antagonists & inhibitors; Receptors, Dopamine D1 - metabolism; Stiffness; Substrate inhibition; substrate stiffness; Substrates; Tamoxifen; Tamoxifen - pharmacology; Tumor Microenvironment
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26026

Existing studies on the mechanism of cell volume regulation are mainly relevant to ion channels and osmosis in extracellular fluid. Recently, accumulating evidence has shown that cellular mechanical microenvironment also influences the cell volume. Herein, we investigated the regulation of substrate stiffness on the cell volume homeostasis of MCF‐7 cells and their following migration behaviors. We found that cell volume increases with increasing substrate stiffness, which could be affected by blocking the cell membrane anion permeability and dopamine receptor. In addition, the cell migration is significantly inhibited by decreasing the cell volume using tamoxifen and such inhibition effect on migration is enhanced by increasing substrate stiffness. The cell membrane anion permeability might be the linker between cellular mechanical microenvironment and cellular volume homeostasis regulation. This work revealed the regulation of substrate stiffness on cell volume homeostasis for the first time, which would provide a new perspective into the understanding of cancer metastasis and a promising anti‐cancer therapy through regulation of cell volume homeostasis. This work revealed the regulation of substrate stiffness on cell volume homeostasis for the first time, which could be affected by blocking the cell membrane anion permeability and dopamine receptor. In addition, the cell migration is significantly inhibited by decreasing the cell volume using tamoxifen and such inhibition effect on migration is enhanced by increasing substrate stiffness.