Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a ″Watch-and-Wait″� Approach to Cancer

Abstract

Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open up new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME-driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cell-specific manner. Here, based on our previous data, we provide a framework through which such gene expression changes in response to external mechanical forces can be understood during cancer progression. Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a “watch-and-wait” approach. We attempt to address both normal brain microenvironment and tumor microenvironment as both works together, intertwining in pathology and physiology – a balance that needs to be maintained for the “watch-and-wait” approach to cancer. Thus, this review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts to unify apparently separate entities in a complex biological web, network, and system in a realistic and practical manner, i.e., to bridge basic research with clinical application.

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

“…In normal tissues a homeostatic environment is maintained with most cells maintaining their differentiated states and well defined boundaries between tissue compartments. Tumor initiation and progression is associated with disruption of tissue architecture and organization [ 99 , 100 , 101 ]. An environment that was tumor inhibiting becomes permissive and supportive to tumor growth and metastasis [ 80 , 83 , 90 , 102 , 103 , 104 ].…”

Mechanical Regulation Underlies Effects of Exercise on Serotonin-Induced Signaling in the Prefrontal Cortex Neurons

“…Collectively, the loss of suppressive effect of PHM on HTR ( Figures 5B and 5C) is likely to result from hydrogel-mediated alteration in interstitial fluid dynamics. Still, there may be unspecified effects of hydrogel introduction on the PFC neurons, particularly given that the hydrogel may alter the stiffness of extracellular matrix and the elasticity of the brain, which is known to affect the neurological physiology, pathology, and development (Li et al, 2017).…”

Single-cell transcriptomes reveal the mechanism for a breast cancer prognostic gene panel

“…To secure efficacy of cell cycle-based therapy, physicians need to track down the spatiotemporal changes of each cell within breast tissue at molecular, cellular and tissue levels. Technologies (next generation sequencing technology, single-cell mRNA sequencing for single-cell gene signatures, and positioning imaging system for biomarkers [ 17 ]) can capture the spatiotemporal information that defines the cell-by-cell origins of breast cancer, in its earliest phases that acquire genetic alterations, potential for early cancer detection, leading to cancer prevention, slowing cancer progression or early management for co-survival with cancer [ 11 ], before it turns into a life-threatening cancer burden [ 18 ]. Such non-invasive imaging-based analysis of spatiotemporal gene-expression patterns [ 17 ] in single cells may shed new light onto the developmental processes that lead to “wait-and-watch” approaches [ 18 ], by defining “therapeutic windows” [ 19 ], with multiple check points of the full spectrum of cellular diversity that exists in the human body, in cancer initiation, progression and metastasis.…”