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High blood flow shear stress values are associated with circulating tumor cells cluster disaggregation in a multi-channel microfluidic device.
Marrella, Alessandra; Fedi, Arianna; Varani, Gabriele; Vaccari, Ivan; Fato, Marco; Firpo, Giuseppe; Guida, Patrizia; Aceto, Nicola; Scaglione, Silvia.
Afiliación
  • Marrella A; National Research Council (CNR), Institute of Electronic, Computer and Telecommunications (IEIIT), Genoa, Italy.
  • Fedi A; National Research Council (CNR), Institute of Electronic, Computer and Telecommunications (IEIIT), Genoa, Italy.
  • Varani G; Department of Computer Science, Bioengineering, Robotics and Systems Engineering, University of Genoa, Genoa, Italy.
  • Vaccari I; National Research Council (CNR), Institute of Electronic, Computer and Telecommunications (IEIIT), Genoa, Italy.
  • Fato M; National Research Council (CNR), Institute of Electronic, Computer and Telecommunications (IEIIT), Genoa, Italy.
  • Firpo G; Department of Computer Science, Bioengineering, Robotics and Systems Engineering, University of Genoa, Genoa, Italy.
  • Guida P; Department of Physics, University of Genoa, Genoa, Italy.
  • Aceto N; Department of Physics, University of Genoa, Genoa, Italy.
  • Scaglione S; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
PLoS One ; 16(1): e0245536, 2021.
Article en En | MEDLINE | ID: mdl-33444361
Metastasis represents a dynamic succession of events involving tumor cells which disseminate through the organism via the bloodstream. Circulating tumor cells (CTCs) can flow the bloodstream as single cells or as multicellular aggregates (clusters), which present a different potential to metastasize. The effects of the bloodstream-related physical constraints, such as hemodynamic wall shear stress (WSS), on CTC clusters are still unclear. Therefore, we developed, upon theoretical and CFD modeling, a new multichannel microfluidic device able to simultaneously reproduce different WSS characterizing the human circulatory system, where to analyze the correlation between SS and CTC clusters behavior. Three physiological WSS levels (i.e. 2, 5, 20 dyn/cm2) were generated, reproducing values typical of capillaries, veins and arteries. As first validation, triple-negative breast cancer cells (MDA-MB-231) were injected as single CTCs showing that higher values of WSS are correlated with a decreased viability. Next, the SS-mediated disaggregation of CTC clusters was computationally investigated in a vessels-mimicking domain. Finally, CTC clusters were injected within the three different circuits and subjected to the three different WSS, revealing that increasing WSS levels are associated with a raising clusters disaggregation after 6 hours of circulation. These results suggest that our device may represent a valid in vitro tool to carry out systematic studies on the biological significance of blood flow mechanical forces and eventually to promote new strategies for anticancer therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Mecánico / Resistencia al Corte / Dispositivos Laboratorio en un Chip / Hemodinámica / Células Neoplásicas Circulantes Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Mecánico / Resistencia al Corte / Dispositivos Laboratorio en un Chip / Hemodinámica / Células Neoplásicas Circulantes Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos