Low-intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial-to-mesenchymal transition of colorectal cancer cells.

Author: Lucchetti D1,2, Perelli L2, Colella F2, Ricciardi-Tenore C2, Scoarughi G3, Barbato G3, Boninsegna A2, De Maria R1,2, Sgambato A2,4
Affiliation:
1Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.
2Institute of General Pathology, Università Cattolica del Sacro Cuore, Roma, Italy.
3Promedica Bioelectronics srl, Roma, Italy.
4Scientific Direction, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, Italy.
Conference/Journal: J Cell Physiol.
Date published: 2020 Jan 22
Other: Special Notes: doi: 10.1002/jcp.29423. [Epub ahead of print] , Word Count: 255


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.

© 2020 Wiley Periodicals, Inc.

KEYWORDS: EMT; LIPUS; colon cancer differentiation; extracellular vesicles; motility

PMID: 31967331 DOI: 10.1002/jcp.29423

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