1. Dissecting Breast Cancer Circulating Tumor Cells Competence via Modelling Metastasis in Zebrafish
- Author
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Anas Chaachou, Laura Sánchez, Santiago Ramón y Cajal, Pablo Hurtado, Inés Martínez-Pena, Carmen Abuín, Roberto Piñeiro, Nuria Carmona-Ule, Javier Hernández-Losa, Ana B. Dávila-Ibáñez, Rafael López-López, Miguel Abal, Institut Català de la Salut, [Martínez-Pena I] Roche-Chus Joint Unit, Translational Medical Oncology Group, Oncomet, Health Research Institute of Santiago de Compostela, Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain. CIBERONC, Centro de Investigación Biomédica en Red Cáncer, 28029 Madrid, Spain [Hurtado P, Carmona-Ule N, Abuín C, Dávila-Ibáñez AB] Roche-Chus Joint Unit, Translational Medical Oncology Group, Oncomet, Health Research Institute of Santiago de Compostela, Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain. [Sánchez L] Departamento de Zoología, Genética y Antropología Física, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain. [Chaachou A] Grup de Patologia Molecular Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Hernández-Losa J, Ramón y Cajal S] CIBERONC, Centro de Investigación Biomédica en Red Cáncer, 28029 Madrid, Spain. Grup de Patologia Molecular Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Embryo, Nonmammalian ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Neoplasms::Neoplastic Processes::Neoplasm Metastasis::Neoplastic Cells, Circulating [DISEASES] ,Metastasis ,Mice ,Circulating tumor cell ,Biology (General) ,Neoplasm Metastasis ,Zebrafish ,Spectroscopy ,in vitro models ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,biology ,General Medicine ,Cell cycle ,Neoplastic Cells, Circulating ,Primary tumor ,Computer Science Applications ,Mama - Càncer - Models animals ,Chemistry ,MCF-7 Cells ,Cèl·lules canceroses ,in vivo models ,Female ,CTC-clusters ,QH301-705.5 ,circulating tumor cells (CTCs) ,Breast Neoplasms ,cell survival ,Catalysis ,Article ,Inorganic Chemistry ,Breast cancer ,breast cancer ,Metàstasi ,Cell Line, Tumor ,medicine ,metastasis ,Animals ,Humans ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Organic Chemistry ,Gene signature ,medicine.disease ,biology.organism_classification ,zebrafish ,Disease Models, Animal ,neoplasias::procesos neoplásicos::metástasis neoplásica::células neoplásicas circulantes [ENFERMEDADES] ,Cancer research ,Investigative Techniques::Models, Animal::Investigative Techniques::Disease Models, Animal [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,técnicas de investigación::modelos animales::técnicas de investigación::modelos de enfermedad en animales [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Homing (hematopoietic) - Abstract
Cáncer de mama; Metástasis; Pez cebra Càncer de mama; Metàstasi; Peix zebra Breast cancer; Metastasis; 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 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. 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).
- Published
- 2021