Cell stiffness predicts cancer cell sensitivity to ultrasound as a selective superficial cancer therapy

Bergman, Eden; Goldbart, Riki; Traitel, Tamar; Amar-Lewis, Eliz; Zorea, Jonathan; Yegodayev, Ksenia M.; Alon, Irit; Rankovic, Sanela; Krieger, Yuval; Rousso, Itay; Elkabets, Moshe; Kost, Joseph

doi:10.1002/btm2.10226

Cited by 10 publications

(8 citation statements)

References 80 publications

(149 reference statements)

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“…Our results are comparable to those of previous studies on cancer cells. Low-intensity pulsed ultrasound stimulation at 20 kHz of frequency and energies between 2.8 and 6.6 J/ cm 2 also decreased the cell elastic modulus for squamous cells, carcinomas, and melanomas, indicating that cancer cells were less stiff than noncancerous cells [63].…”

Section: Discussionmentioning

confidence: 96%

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Effect of Therapeutic Ultrasound on the Mechanical and Biological Properties of Fibroblasts

Cárdenas-Sandoval

Pastrana

Ávila

et al. 2022

Regen. Eng. Transl. Med.

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Purpose This paper explores the effect of therapeutic ultrasound on the mechanical and biological properties of ligament fibroblasts. Methods and Results We assessed pulsed ultrasound doses of 1.0 and 2.0 W/cm2 at 1 MHz frequency for five days on ligament fibroblasts using a multidisciplinary approach. Atomic force microscopy showed a decrease in cell elastic modulus for both doses, but the treated cells were still viable based on flow cytometry. Finite element method analysis exhibited visible cytoskeleton displacements and decreased harmonics in treated cells. Colorimetric assay revealed increased cell proliferation, while scratch assay showed increased migration at a low dose. Enzyme-linked immunoassay detected increased collagen and fibronectin at a high dose, and immunofluorescence imaging technique visualized β-actin expression for both treatments. Conclusion Both doses of ultrasound altered the fibroblast mechanical properties due to cytoskeletal reorganization and enhanced the regenerative and remodeling stages of cell repair. Lay Summary Knee ligament injuries are a lesion of the musculoskeletal system frequently diagnosed in active and sedentary lifestyles in young and older populations. Therapeutic ultrasound is a rehabilitation strategy that may lead to the regenerative and remodeling of ligament wound healing. This research demonstrated that pulsed therapeutic ultrasound applied for 5 days reorganized the ligament fibroblasts structure to increase the cell proliferation and migration at a low dose and to increase the releasing proteins that give the stiffness of the healed ligament at a high dose. Future Works Future research should further develop and confirm that therapeutic ultrasound may improve the regenerative and remodeling stages of the ligament healing process applied in clinical trials in active and sedentary lifestyles in young and older populations. Graphical abstract

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Section: Discussionmentioning

confidence: 96%

“…Specifically, Wang et al observed autophagy, apoptosis, and mitochondrial structural and functional damage to cancer cells [70]. Bergman et al also demonstrated that the viability decreased in cancer cells due to a lesser frequency applied in ultrasound (20 kHz) [63].…”

Section: Discussionmentioning

confidence: 99%

Effect of Therapeutic Ultrasound on the Mechanical and Biological Properties of Fibroblasts

Cárdenas-Sandoval

Pastrana

Ávila

et al. 2022

Regen. Eng. Transl. Med.

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“…Hence, particular 65,79 (b) mechanical stretch, 151,152,160 (c) high-intensity ultrasound frequency, 45,75,136,138,139 (d) and low-intensity pulsed ultrasound. 55,68,70,71 . (e) Targeting cells associated with tumor-associated T-cells, 114,119 dendritic cells, 130,132,138 tumor-associated macrophages, 149 and cancer-associated fibroblasts.…”

Section: Extracellular Matrix (Ecm)mentioning

confidence: 99%

“…Schematic representation of mechanobiology-based therapies. Targeting cancer cells by mechanical perturbations like (a) shock wave, , (b) mechanical stretch, ,, (c) high-intensity ultrasound frequency, ,,,, (d) and low-intensity pulsed ultrasound. ,,, . (e) Targeting cells associated with tumor-associated T-cells, , dendritic cells, ,, tumor-associated macrophages, and cancer-associated fibroblasts .…”

Section: Mechanobiological Strategies Targeting the Tumor Microenviro...mentioning

confidence: 99%

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Mechanobiological Strategies to Augment Cancer Treatment

Kumari,

Veena,

Luha

et al. 2023

ACS Omega

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Cancer cells exhibit aberrant extracellular matrix mechanosensing due to the altered expression of mechanosensory cytoskeletal proteins. Such aberrant mechanosensing of the tumor microenvironment (TME) by cancer cells is associated with disease development and progression. In addition, recent studies show that such mechanosensing changes the mechanobiological properties of cells, and in turn cells become susceptible to mechanical perturbations. Due to an increasing understanding of cell biomechanics and cellular machinery, several approaches have emerged to target the mechanobiological properties of cancer cells and cancer-associated cells to inhibit cancer growth and progression. In this Perspective, we summarize the progress in developing mechano-based approaches to target cancer by interfering with the cellular mechanosensing machinery and overall TME.

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Pin1/YAP pathway mediates matrix stiffness‐induced epithelial–mesenchymal transition driving cervical cancer metastasis via a non‐Hippo mechanism

Yang

Zang

et al. 2022

Bioengineering & Transla Med

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Cervical cancer metastasis is an important cause of death in cervical cancer. Previous studies have shown that epithelial–mesenchymal transition (EMT) of tumors promotes its invasive and metastatic capacity. Alterations in the extracellular matrix (ECM) and mechanical signaling are closely associated with cancer cell metastasis. However, it is unclear how matrix stiffness as an independent cue triggers EMT and promotes cervical cancer metastasis. Using collagen‐coated polyacrylamide hydrogel models and animal models, we investigated the effect of matrix stiffness on EMT and metastasis in cervical cancer. Our data showed that high matrix stiffness promotes EMT and migration of cervical cancer hela cell lines in vitro and in vivo. Notably, we found that matrix stiffness regulates yes‐associated protein (YAP) activity via PPIase non‐mitotic a‐interaction 1 (Pin1) with a non‐Hippo mechanism. These data indicate that matrix stiffness of the tumor microenvironment positively regulates EMT in cervical cancer through the Pin1/YAP pathway, and this study deepens our understanding of cervical cancer biomechanics and may provide new ideas for the treatment of cervical cancer.

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Cell stiffness predicts cancer cell sensitivity to ultrasound as a selective superficial cancer therapy

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 10 publications

References 80 publications

Effect of Therapeutic Ultrasound on the Mechanical and Biological Properties of Fibroblasts

Effect of Therapeutic Ultrasound on the Mechanical and Biological Properties of Fibroblasts

Mechanobiological Strategies to Augment Cancer Treatment

Pin1/YAP pathway mediates matrix stiffness‐induced epithelial–mesenchymal transition driving cervical cancer metastasis via a non‐Hippo mechanism

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