Dissecting Breast Cancer Circulating Tumor Cells Competence via Modelling Metastasis in Zebrafish

Background: Cancer metastasis is a deathly process, and a better understanding of the different steps is needed. The shedding of circulating tumor cells (CTCs) and CTC-cluster from the primary tumor, its survival in circulation, and homing are key events of the metastasis cascade. In vitro models of...

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Detalles Bibliográficos
Autores: Martínez-Pena, Inés|||0000-0001-5595-3405, Hurtado Blanco, P., Carmona-Ule, Nuria|||0000-0001-6312-6530, Abuín, Carmen|||0000-0002-6902-4161, Dávila-Ibáñez, Ana Belén|||0000-0002-9906-5458, Sánchez-García, Laura|||0000-0002-8420-1701, Abal Posada, Miguel|||0000-0003-3533-7781, Chaachou, Anas, Hernandez-Losa, Javier|||0000-0003-1526-3201, Ramón y Cajal, Santiago|||0000-0002-3867-1390, López López, Rafael|||0000-0003-1315-655X, Piñeiro, Roberto|||0000-0001-9479-139X
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:dnet:uabarcelona_::22560b145080a23996f58b09bc6b1d90
Acceso en línea:https://ddd.uab.cat/record/327701
https://dx.doi.org/urn:doi:10.3390/ijms22179279
Access Level:acceso abierto
Palabra clave:Breast cancer
Metastasis
circulating tumor cells (CTCs)
CTC-clusters
Zebrafish
In vitro models
In vivo models
Cell survival
Descripción
Sumario:Background: Cancer metastasis is a deathly process, and a better understanding of the different steps is needed. The shedding of circulating tumor cells (CTCs) and CTC-cluster from the primary tumor, its survival in circulation, and homing are key events of the metastasis cascade. In vitro models of CTCs and in vivo models of metastasis represent an excellent opportunity to delve into the behavior of metastatic cells, to gain understanding on how secondary tumors appear. Methods: Using the zebrafish embryo, in combination with the mouse and in vitro assays, as an in vivo model of the spatiotemporal development of metastases, we study the metastatic competency of breast cancer CTCs and CTC-clusters and the molecular mechanisms. Results: CTC-clusters disseminated at a lower frequency than single CTCs in the zebrafish and showed a reduced capacity to invade. A temporal follow-up of the behavior of disseminated CTCs showed a higher survival and proliferation capacity of CTC-clusters, supported by their increased resistance to fluid shear stress. These data were corroborated in mouse studies. In addition, a differential gene signature was observed, with CTC-clusters upregulating cell cycle and stemness related genes. Conclusions: The zebrafish embryo is a valuable model system to understand the biology of breast cancer CTCs and CTC-clusters.

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