RT Journal Article T1 Dissecting Breast Cancer Circulating Tumor Cells Competence via Modelling Metastasis in Zebrafish A1 Hurtado, Pablo A1 Carmona-Ule, Nuria A1 Dávila Ibáñez, Ana Belén A1 Sánchez Piñón, Laura A1 Abal Posada, Miguel A1 Chaachou, Anas A1 Hernandez-Losa, Javier A1 Ramon y Cajal, Santiago A1 Piñeiro, Roberto A1 Martínez Pena, Inés A1 Abuín Redondo, Carmen A1 López López, Rafael K1 CTC-clusters K1 Breast cancer K1 Metastasis K1 Circulating tumor cells (CTCs) K1 Zebrafish K1 In vitro models K1 In vivo models K1 Cell survival AB 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. PB MDPI SN 1422-0067 YR 2021 FD 2021-08-27 LK http://hdl.handle.net/10347/32018 UL http://hdl.handle.net/10347/32018 LA eng NO Martínez-Pena, I.; Hurtado, P.; Carmona-Ule, N.; Abuín, C.; Dávila-Ibáñez, A.B.; Sánchez, L.; Abal, M.; Chaachou, A.; Hernández-Losa, J.; Cajal, S.R.y.; et al. Dissecting Breast Cancer Circulating Tumor Cells Competence via Modelling Metastasis in Zebrafish. Int. J. Mol. Sci. 2021, 22, 9279. https://doi.org/10.3390/ijms22179279 NO This work was supported by Roche-Chus Joint Unit (IN853B 2018/03) funded by Axencia Galega de Innovación (GAIN), Consellería de Economía, Emprego e Industria. I.M.-P. is funded by the Training Program for Academic Staff fellowship (FPU16/01018), from the Ministry of Education and Vocational Training, Spanish Government. P.H. is funded by a Predoctoral fellowship (IN606A-2018/019) from Axencia Galega de Innovación (GAIN, Xunta de Galicia). N.C.-U. is funded by Axudas Predoutorais do IDIS (Instituto de Investigación Sanitaria de Santiago). DS Minerva RD 7 jun 2026