Tumor stem cells fuse with monocytes to form highly invasive tumor-hybrid cells.

Autor:	Aguirre LA; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Montalbán-Hernández K; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Avendaño-Ortiz J; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Centre for Biomedical Research Network of Respiratory Diseases (CIBERES), Madrid, Spain., Marín E; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Lozano R; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Toledano V; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Centre for Biomedical Research Network of Respiratory Diseases (CIBERES), Madrid, Spain., Sánchez-Maroto L; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Terrón V; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Valentín J; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Pulido E; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Casalvilla JC; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Rubio C; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Diekhorst L; Department of Neurology and Stroke Centre, Neuroscience and Cerebrovascular Research Laboratory, IdiPAZ, La Paz University Hospital, Autonomous University of Madrid, Madrid, Spain., Laso-García F; Department of Neurology and Stroke Centre, Neuroscience and Cerebrovascular Research Laboratory, IdiPAZ, La Paz University Hospital, Autonomous University of Madrid, Madrid, Spain., Del Fresno C; Immunobiology Laboratory, National Centre for Cardiovascular Research (CNIC), Madrid, Spain., Collazo-Lorduy A; Oncology Department, Research Foundation HM Hospitals, Madrid, Spain., Jiménez-Munarriz B; Oncology Department, Research Foundation HM Hospitals, Madrid, Spain., Gómez-Campelo P; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Llanos-González E; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Fernández-Velasco M; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Centre for Biomedical Research Network, CIBER-CV, Madrid, Spain., Rodríguez-Antolín C; Biomarkers and Experimental Therapeutics in Cancer Group, IdiPAZ, La Paz University Hospital, Madrid, Spain., Pérez de Diego R; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Laboratory of Immunogenetics of Human Diseases, IdiPAZ, Madrid, Spain., Cantero-Cid R; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Hernádez-Jimenez E; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Álvarez E; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain., Rosas R; Biomarkers and Experimental Therapeutics in Cancer Group, IdiPAZ, La Paz University Hospital, Madrid, Spain., Dies López-Ayllón B; Biomarkers and Experimental Therapeutics in Cancer Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Laboratory of Experimental Models of Human Diseases, Biomedical Research Institute CSIC/UAM, Madrid, Spain.; Centre for Biomedical Research Network, CIBERER, Madrid, Spain., de Castro J; Biomarkers and Experimental Therapeutics in Cancer Group, IdiPAZ, La Paz University Hospital, Madrid, Spain., Wculek SK; Immunobiology Laboratory, National Centre for Cardiovascular Research (CNIC), Madrid, Spain., Cubillos-Zapata C; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Centre for Biomedical Research Network of Respiratory Diseases (CIBERES), Madrid, Spain., Ibáñez de Cáceres I; Biomarkers and Experimental Therapeutics in Cancer Group, IdiPAZ, La Paz University Hospital, Madrid, Spain., Díaz-Agero P; Thoracic Surgery Service, IdiPAZ, La Paz University Hospital, Madrid, Spain., Gutiérrez Fernández M; Department of Neurology and Stroke Centre, Neuroscience and Cerebrovascular Research Laboratory, IdiPAZ, La Paz University Hospital, Autonomous University of Madrid, Madrid, Spain., Paz de Miguel M; Cell Engineering Laboratory, IdiPAZ, La Paz University Hospital, Madrid, Spain., Sancho D; Immunobiology Laboratory, National Centre for Cardiovascular Research (CNIC), Madrid, Spain., Schulte L; Institute for Lung Research/iLung, Research Group 'Rna-biology of Inflammation & Infection,' Philipps University, Marburg, Germany., Perona R; Biomarkers and Experimental Therapeutics in Cancer Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Laboratory of Experimental Models of Human Diseases, Biomedical Research Institute CSIC/UAM, Madrid, Spain.; Centre for Biomedical Research Network, CIBERER, Madrid, Spain., Belda-Iniesta C; Oncology Department, Research Foundation HM Hospitals, Madrid, Spain., Boscá L; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Centre for Biomedical Research Network, CIBER-CV, Madrid, Spain.; Laboratory of Experimental Models of Human Diseases, Biomedical Research Institute CSIC/UAM, Madrid, Spain., López-Collazo E; The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain.; Centre for Biomedical Research Network of Respiratory Diseases (CIBERES), Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2020 Jun 16; Vol. 9 (1), pp. 1773204. Date of Electronic Publication: 2020 Jun 16.
DOI:	10.1080/2162402X.2020.1773204
Abstrakt:	The 'cancer cell fusion' theory is controversial due to the lack of methods available to identify hybrid cells and to follow the phenomenon in patients. However, it seems to be one of the best explanations for both the origin and metastasis of primary tumors. Herein, we co-cultured lung cancer stem cells with human monocytes and analyzed the dynamics and properties of tumor-hybrid cells (THC), as well as the molecular mechanisms beneath this fusion process by several techniques: electron-microscopy, karyotyping, CRISPR-Cas9, RNA-seq, immunostaining, signaling blockage, among others. Moreover, mice models were assessed for in vivo characterization of hybrids colonization and invasiveness. Then, the presence of THCs in bloodstream and samples from primary and metastatic lesions were detected by FACS and immunofluorescence protocols, and their correlations with TNM stages established. Our data indicate that the generation of THCs depends on the expression of CD36 on tumor stem cells and the oxidative state and polarization of monocytes, the latter being strongly influenced by microenvironmental fluctuations. Highly oxidized M2-like monocytes show the strongest affinity to fuse with tumor stem cells. THCs are able to proliferate, colonize and invade organs. THC-specific cell surface signature CD36 + CD14 + PANK + allows identifying them in matched primary tumor tissues and metastases as well as in bloodstream from patients with lung cancer, thus functioning as a biomarker. THCs levels in circulation correlate with TNM classification. Our results suggest that THCs are involved in both origin and spread of metastatic cells. Furthermore, they might set the bases for future therapies to avoid or eradicate lung cancer metastasis. (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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