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Review
. 2019 Apr;12(1):17-27.
doi: 10.1007/s12307-019-00222-4. Epub 2019 Apr 19.

Mechanobiology of Cancer Stem Cells and Their Niche

Ankit Roy Choudhury  1 , Surabhi Gupta  1 , Pradeep Kumar Chaturvedi  1 , Neeraj Kumar  1 , Deepak Pandey  2
Affiliations
Review

Mechanobiology of Cancer Stem Cells and Their Niche

Ankit Roy Choudhury et al. Cancer Microenviron. 2019 Apr.

Abstract

Though the existence of cancer stem cells remained enigmatic initially, over the time their participation in tumorigenesis and tumor progression has become highly evident. Today, they are also appreciated as the causal element for tumor heterogeneity and drug-resistance. Cancer stem cells activate a set of molecular pathways some of which are triggered by the unique mechanical properties of the tumor tissue stroma. A relatively new field called mechanobiology has emerged, which aims to critically evaluate the mechanical properties associated with biological events like tissue morphogenesis, cell-cell or cell-matrix interactions, cellular migration and also the development and progression of cancer. Development of more realistic model systems and biophysical instrumentation for observation and manipulation of cell-dynamics in real-time has invoked a hope for some novel therapeutic modalities against cancer in the future. This review discusses the fundamental concepts of cancer stem cells from an intriguing viewpoint of mechanobiology and some important breakthroughs to date.

Keywords: Mechanotransduction; Niche; Stem cells; Stiffness; Stromal remodeling.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Schematic representation of the two familiar models of cancer initiation and progression. a. Stochastic model: According to this model, each cancer cell of a tumor is equally potent to continuously divide and form tumor. b. Hierarchical model: According to this model, only few cells called cancer stem cells of a tumor are capable of dividing, differentiating and reinitiating tumor. Other cells are not generally able to perpetuate a tumor, though they possess the ability to dedifferentiate into cancer stem cells
Fig. 2
Fig. 2
Mechanosensory molecular pathways in cancer stem cell. Mechanical stress induced by stiffened ECM, composed of collagen, laminin, fibronectin, hyaluronan etc. can be sensed by mechanosensors (integrins, laminin, CD44 receptors, syndecans, DDRs, GPCRs etc.) and transduced to induce pathways specific for CSC survival, self renewal, drug resistance and progression. DDR: discoidin domain receptor; GPCR: G protein coupled rector; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; FAK: focal adhesion kinase; RhoGDI: Rho GDP-dissociation inhibitor; MLCK: Myosin light-chain kinase; MLC: Myosin light-chain; PKA, PKC: Protein kinase A, C; ERK: extracellular signal-regulated kinase
Fig. 3
Fig. 3
Model systems and platforms commonly used in mechanobiological experiments
See this image and copyright information in PMC

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