5037 - CXCR4, CCR2 and CCR5 expression in subsets of tumor cells with stem and/or EMT features

Background

Numerous investigations have been focused on the role of CXCR4, CCR2 and CCR5 in solid tumors, including breast cancer. These chemokine receptors make cancer cells move out of the circulation and traffic into organs with high amounts of chemokines, and thus forming metastases. In this connection, the objective of our stady was to investigate CXCR4, CCR2 and CCR5 expression in subsets of tumor cells with stem and/or EMT features in primary tumor and peripheral blood in breast cancer patients.

Methods

Twenty-three patients with breast cancer, between 29 and 69 years of age, were included in this study. Five-color confocal microscopy was used to investigate tumor cells with stem and/or EMT features, CXCR4, CCR2 and CCR5 expression in primary tumor. Flow cytometry was used to analyze the similar phenotypes of circulating tumor cells (CTC). All patients signed an informed consent for voluntary participation.

Results

In the primary tumor, CXCR4 was expressed on subsets of non-stem and stem-like tumor cells with EMT features. CCR5 was more often expressed by tumor cells with stem and EMT features. The count of such cells in the tumor decreased after neoadjuvant chemotherapy (NACT). CK7+CD45-CD44-CCR2+ and CK7+CD45-CD44-CXCR4+ CTC (without stem features) were detected in breast cancer patients with and without NACT. At the same time, the count of non-stem CXCR4+ CTC was significantly higher in the blood of patients after NACT. CK7+CD45-CD44-N-cadh+CCR5+ CTC (with EMT features) were more frequent in the blood of breast cancer patients after NACT, and its count was significantly higher. It is interesting to note that stem-like CTC didn’t express CCR2 and CCR5. Stem-like CXCR4+ CTC were rarely detected and had no EMT features in patients, regardless of the NACT performance. The count of CCR5+ tumor cells without stem and EMT features correlates with the count of non-stem CCR5+ CTC. The count of CXCR4+ tumor cells with stem and EMT features correlates with the count of non-stem CXCR4+ CTC with EMT features.

Conclusions

Thus, the potency for recruitment into the circulation is found in tumor cells with EMT features, regardless of the stemness status. The study was supported by the Russian Science Foundation (grant 19-75-30016).

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Russian Science Foundation.

Disclosure

All authors have declared no conflicts of interest.