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

SIMPLE SUMMARY: Colorectal cancer survival rates strongly decrease from initial to more advanced stages, primarily because of the occurrence of metastatic lesions. In this line, the search for clinical markers is of critical need. The aim of our study was to examine in vitro generated colorectal tumour hybrid cells (THCs) as a fusion between colorectal cancer (CRC) stem cells and human monocytes, as well as to evaluate their presence in tissue and blood samples from CRC patients. THCs, defined as CD45(+)CD14(+)EpCAM(+), showed enhanced migratory, proliferative and immune evasion abilities compared to their parental cells. In a retrospective cohort of 23 patients, our data showed the potential relevance of resident tissue THCs in the generation of distant metastases. In addition, in a prospective cohort of 38 patients, our data confirmed the correlation between circulating THCs and sSIGLEC5 levels, a molecule which has already been previously described as a marker of poor prognosis in CRC patients. Altogether, our findings indicate that the number of THCs could serve as a novel biomarker for metastasis prediction in colorectal cancer patients. ABSTRACT: Background: The cancer cell fusion theory could be one of the best explanations for the metastasis from primary tumours. 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.