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

Author
Aguirre, Luis Augusto; Montalbán-Hernández, Karla; Avendaño-Ortiz, José; Marín, Elvira; Lozano, Roberto; Toledano, Víctor; Sánchez-Maroto, Laura; Terrón, Verónica; Valentín, Jaime; Pulido, Elisa; Casalvilla, José Carlos; Rubio, Carolina; Diekhorst, Luke; Laso-García, Fernando; del Fresno, Carlos; Collazo-Lorduy, Ana; Jiménez-Munarriz, Beatriz; Gómez-Campelo, Paloma; Llanos-González, Emilio; Fernández-Velasco, María; Rodríguez-Antolín, Carlos; Pérez de Diego, Rebeca; Cantero-Cid, Ramón; Hernádez-Jimenez, Enrique; Álvarez, Enrique; Rosas, Rocío; dies López-Ayllón, Blanca; de Castro, Javier; Wculek, Stefanie K.; Cubillos-Zapata, Carolina; Ibáñez de Cáceres, Inmaculada; Díaz-Agero, Prudencio; Gutiérrez Fernández, María; Paz de Miguel, María; Sancho, David; Schulte, Leon; Perona, Rosario; Belda-Iniesta, Cristóbal; Boscá, Lisardo; López-Collazo, Eduardo
Entity
UAM. Departamento de Cirugía; Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)
Publisher
Taylor & Francis Group, LLC
Date
2020-06-16
Citation
10.1080/2162402X.2020.1773204
OncoImmunology 9.1 (2020): 1-17
 
 
 
ISSN
2162-4011 (print); 2162-402X (online)
DOI
10.1080/2162402X.2020.1773204
Funded by
Research in the laboratory of EL-C was supported by “Fundación para la Investigación Biomédica La Paz Hospital” ((FIBHULP) and “Fundación Familia Alonso”
Editor's Version
https://doi.org/10.1080/2162402X.2020.1773204
Subjects
Cancer stem cells; CD36; lung cancer; metastasis; monocytes/macrophages; Medicina
URI
http://hdl.handle.net/10486/695220
Rights
© 2020 The Authors

Licencia de Creative Commons
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial 4.0 Internacional.

Abstract

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. + + +
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Google™ Scholar:Aguirre, Luis Augusto - Montalbán-Hernández, Karla - Avendaño-Ortiz, José - Marín, Elvira - Lozano, Roberto - Toledano, Víctor - Sánchez-Maroto, Laura - Terrón, Verónica - Valentín, Jaime - Pulido, Elisa - Casalvilla, José Carlos - Rubio, Carolina - Diekhorst, Luke - Laso-García, Fernando - del Fresno, Carlos - Collazo-Lorduy, Ana - Jiménez-Munarriz, Beatriz - Gómez-Campelo, Paloma - Llanos-González, Emilio - Fernández-Velasco, María - Rodríguez-Antolín, Carlos - Pérez de Diego, Rebeca - Cantero-Cid, Ramón - Hernádez-Jimenez, Enrique - Álvarez, Enrique - Rosas, Rocío - dies López-Ayllón, Blanca - de Castro, Javier - Wculek, Stefanie K. - Cubillos-Zapata, Carolina - Ibáñez de Cáceres, Inmaculada - Díaz-Agero, Prudencio - Gutiérrez Fernández, María - Paz de Miguel, María - Sancho, David - Schulte, Leon - Perona, Rosario - Belda-Iniesta, Cristóbal - Boscá, Lisardo - López-Collazo, Eduardo

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  • Producción científica en acceso abierto de la UAM [18125]

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