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Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells
Author(s) -
Lucchetti Donatella,
Perelli Luigi,
Colella Filomena,
RicciardiTenore Claudio,
Scoarughi Gian Luca,
Barbato Gaetano,
Boninsegna Alma,
De Maria Ruggero,
Sgambato Alessandro
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29423
Subject(s) - motility , epithelial–mesenchymal transition , low intensity pulsed ultrasound , cell growth , flow cytometry , viability assay , microbiology and biotechnology , mesenchymal stem cell , cancer research , cell , colorectal cancer , chemistry , biology , cancer , medicine , immunology , therapeutic ultrasound , ultrasound , biochemistry , metastasis , radiology
Ultrasound (US) offers potentially important opportunities from a therapeutic point of view. Thus, the study of the biological effects of US on cancer cells is important to understand the consequences of these changes on the malignant phenotype. This study aimed to investigate the effects of low‐intensity ultrasound (LIPUS) on the phenotype of colorectal cancer cell lines. Cell proliferation was evaluated by viability test and by evaluation of pERK expression, while cell motility using the scratch test. Cell differentiation was evaluated assessing alkaline phosphatase activity. Epithelial mesenchymal transition was assessed by analyzing the expression of Vimentin and E‐Cadherin. Release and uptake of extracellular vesicles (EVs) were evaluated by flow cytometry. LIPUS effects on the organization of cytoskeleton were analyzed by confocal microscopy and by evaluation of Rho GTPase expression. No alterations in vitality and clonogenicity were observed when the intermediate (0.4 MPa) and the lowest (0.035 MPa) acoustic intensities were administered while the treatment with high intensity (1 MPa) induced a reduction of both cell viability and clonogenicity in both cell lines in a frequency‐dependent manner. LIPUS promoted the differentiation of colon cancer cells, affected epithelial‐to‐mesenchymal transition, promoted the closure of a wound as well as increased the release of EVs compared with untreated cells. LIPUS‐induced increase in cell motility was likely due to a Rho GTPase‐dependent mechanism. Overall, the results obtained warrant further studies on the potential combined effect of LIPUS with differentiating agents and on their potential use in a clinical setting.