Dataset Information

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 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 cellspecific 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 "watchand- 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.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.

SUBMITTER: Li SC

PROVIDER: S-EPMC5587377 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Li Shengwen Calvin SC Vu Long T LT Luo Jane Jianying JJ Zhong Jiang F JF Li Zhongjun Z Dethlefs Brent A BA Loudon William G WG Kabeer Mustafa H MH

Current stem cell research & therapy 20170101 6

<h4>Background</h4>Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open 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 ...[more]

PMID: 28270089

Similar Datasets

Project description:The extracellular matrix (ECM) of the lung provides physical support and key mechanical signals to pulmonary cells. Although lung ECM is continuously subjected to different stretch levels, detailed mechanics of the ECM at the scale of the cell is poorly understood. Here, we developed a new polydimethylsiloxane (PDMS) chip to probe nonlinear mechanics of tissue samples with atomic force microscopy (AFM). Using this chip, we performed AFM measurements in decellularized rat lung slices at controlled stretch levels. The AFM revealed highly nonlinear ECM elasticity with the microscale stiffness increasing with tissue strain. To correlate micro- and macroscale ECM mechanics, we also assessed macromechanics of decellularized rat lung strips under uniaxial tensile testing. The lung strips exhibited exponential macromechanical behavior but with stiffness values one order of magnitude lower than at the microscale. To interpret the relationship between micro- and macromechanical properties, we carried out a finite element (FE) analysis which revealed that the stiffness of the alveolar cell microenvironment is regulated by the global strain of the lung scaffold. The FE modeling also indicates that the scale dependence of stiffness is mainly due to the porous architecture of the lung parenchyma. We conclude that changes in tissue strain during breathing result in marked changes in the ECM stiffness sensed by alveolar cells providing tissue-specific mechanical signals to the cells. STATEMENT OF SIGNIFICANCE: The micromechanical properties of the extracellular matrix (ECM) are a major determinant of cell behavior. The ECM is exposed to mechanical stretching in the lung and other organs during physiological function. Therefore, a thorough knowledge of the nonlinear micromechanical properties of the ECM at the length scale that cells probe is required to advance our understanding of cell-matrix interplay. We designed a novel PDMS chip to perform atomic force microscopy measurements of ECM micromechanics on decellularized rat lung slices at different macroscopic strain levels. For the first time, our results reveal that the microscale stiffness of lung ECM markedly increases with macroscopic tissue strain. Therefore, changes in tissue strain during breathing result in variations in ECM stiffness providing tissue-specific mechanical signals to lung cells.

Project description:ImportanceThe watch-and-wait (WW) strategy aims to spare patients with rectal cancer unnecessary resection.ObjectiveTo analyze the outcomes of WW among patients with rectal cancer who had a clinical complete response to neoadjuvant therapy.Design, setting, and participantsThis retrospective case series analysis conducted at a comprehensive cancer center in New York included patients who received a diagnosis of rectal adenocarcinoma between January 1, 2006, and January 31, 2015. The median follow-up was 43 months. Data analyses were conducted from June 1, 2016, to October 1, 2018.ExposuresPatients had a clinical complete response after completing neoadjuvant therapy and agreed to a WW strategy of active surveillance and possible salvage surgery (n = 113), or patients underwent total mesorectal excision and were found to have a pathologic complete response (pCR) at resection (n = 136).Main outcomes and measuresKaplan-Meier estimates were used for analyses of local regrowth and 5-year rates of overall survival, disease-free survival, and disease-specific survival.ResultsCompared with the 136 patients in the pCR group, the 113 patients in the WW group were older (median [range], 67.2 [32.1-90.9] vs 57.3 [25.0-87.9] years, P < .001) with cancers closer to the anal verge (median [range] height from anal verge, 5.5 [0.0-15.0] vs 7.0 [0.0-13.0] cm). All 22 local regrowths in the WW group were detected on routine surveillance and treated by salvage surgery (20 total mesorectal excisions plus 2 transanal excisions). Pelvic control after salvage surgery was maintained in 20 of 22 patients (91%). No pelvic recurrences occurred in the pCR group. Rectal preservation was achieved in 93 of 113 patients (82%) in the WW group (91 patients with no local regrowths plus 2 patients with local regrowths salvaged with transanal excision). At 5 years, overall survival was 73% (95% CI, 60%-89%) in the WW group and 94% (95% CI, 90%-99%) in the pCR group; disease-free survival was 75% (95% CI, 62%-90%) in the WW group and 92% (95% CI, 87%-98%) in the pCR group; and disease-specific survival was 90% (95% CI, 81%-99%) in the WW group and 98% (95% CI, 95%-100%) in the pCR group. A higher rate of distant metastasis was observed among patients in the WW group who had local regrowth vs those who did not have local regrowth (36% vs 1%, P < .001).Conclusions and relevanceA WW strategy for select rectal cancer patients who had a clinical complete response after neoadjuvant therapy resulted in excellent rectal preservation and pelvic tumor control; however, in the WW group, worse survival was noted along with a higher incidence of distant progression in patients with local regrowth vs those without local regrowth.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets