Colorectal Cancer Stem Cells Fuse with Monocytes to Form Tumour Hybrid Cells with the Ability to Migrate and Evade the Immune System

结直肠癌干细胞与单核细胞融合形成具有迁移和逃避免疫系统能力的肿瘤混合细胞

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作者:Karla Montalbán-Hernández, Ramón Cantero-Cid, José Carlos Casalvilla-Dueñas, José Avendaño-Ortiz, Elvira Marín, Roberto Lozano-Rodríguez, Verónica Terrón-Arcos, Marina Vicario-Bravo, Cristóbal Marcano, Jorge Saavedra-Ambrosy, Julia Prado-Montero, Jaime Valentín, Rebeca Pérez de Diego, Laura Córdoba,

Background

The cancer cell fusion theory could be one of the best explanations for the metastasis from primary tumours.

Conclusions

Our results indicate the generation of a hybrid entity after the in vitro co-culture between CRC stem cells and human monocytes. Moreover, THC numbers present in patients are related to both prognosis and the later spread of metastases in CRC patients.

Methods

Herein, we co-cultured colorectal cancer (CRC) stem cells with human monocytes and analysed the properties of the generated tumour hybrid cells (THCs). The presence of THCs in the bloodstream together with samples from primary and metastatic lesions and their clinical correlations were evaluated in CRC patients and were detected by both FACS and immunofluorescence methods. Additionally, the role of SIGLEC5 as an immune evasion molecule in colorectal cancer was evaluated.

Results

Our data demonstrated the generation of THCs after the in vitro co-culture of CRC stem cells and monocytes. These cells, defined as CD45+CD14+EpCAM+, showed enhanced migratory and proliferative abilities. The THC-specific cell surface signature allows identification in matched primary tumour tissues and metastases as well as in the bloodstream from patients with CRC, thus functioning as a biomarker. Moreover, SIG-LEC5 expression on in vitro generated THCs has shown to be involved in the mechanism for immune evasion. Additionally, sSIGLEC5 levels correlated with THC numbers in the prospective cohort of patients. Conclusions: Our results indicate the generation of a hybrid entity after the in vitro co-culture between CRC stem cells and human monocytes. Moreover, THC numbers present in patients are related to both prognosis and the later spread of metastases in CRC patients.

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