2024-03-29T05:03:06Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/128702023-10-06T09:23:28Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
00925njm 22002777a 4500
dc
Aguirre, Luis A.
author
Montalbán-Hernández, Karla
author
Avendaño-Ortiz, José
author
Marín, Elvira
author
Lozano, Roberto
author
Toledano, Víctor
author
Sánchez-Maroto, Laura
author
Terrón, Verónica
author
Valentín, Jaime
author
Pulido, Elisa
author
Casalvilla, José Carlos
author
Rubio, Carolina
author
Diekhorst, Luke
author
Laso-García, Fernando
author
del Fresno, Carlos
author
Collazo-Lorduy, Ana
author
Jiménez-Munarriz, Beatriz
author
Gómez-Campelo, Paloma
author
Llanos-González, Emilio
author
Fernández-Velasco, María
author
Rodríguez-Antolín, Carlos
author
Pérez de Diego, Rebeca
author
Cantero-Cid, Ramón
author
Hernádez-Jimenez, Enrique
author
Álvarez, Enrique
author
Rosas, Rocío
author
Dies López-Ayllón, Blanca
author
de Castro, Javier
author
Wculek, Stefanie K
author
Cubillos-Zapata, Carolina
author
Ibanez de Caceres, Inmaculada
author
Díaz-Agero, Prudencio
author
Gutiérrez Fernández, María
author
Paz de Miguel, María
author
Sancho, David
author
Schulte, Leon
author
Perona, Rosario
author
Belda-Iniesta, Cristobal
author
Boscá, Lisardo
author
López-Collazo, Eduardo
author
2020-09
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.
Oncoimmunology. 2020; 9(1):1773204
2162-4011
http://hdl.handle.net/20.500.12105/12870
32923132
10.1080/2162402X.2020.1773204
Oncoimmunology
Tumor stem cells fuse with monocytes to form highly invasive tumor-hybrid cells.