Tumor Properties Mediate the Relationship between Peripheral Blood Monocytes and Tumor-Associated Macrophages in Breast Cancer

Abstract

In cancer patients, circulating monocytes show functional alterations. Since monocytes are precursors of tumor-associated macrophages (TAMs), TAMs ensuring tumor viability are potentially replenished through the recruitment of monocytes with specific properties. We demonstrated that locoregional metastasis and circulating factors, such as CD45-EpCAM + CD44 + CD24-/low circulating tumor cells, and serum MCP-1 and HMGB1 were statistically associated with modulation of the monocyte features in breast cancer patients. The count of circulating CD45-EpCAM + cells correlated with CD68+, CD163 + monocyte in blood, and with density of CD68 + TAM in breast cancer tumors. Overall, the relationship between monocytes and TAMs is mediated by the tumor in breast cancer patients.

Keywords:

• Breast cancer
• monocytes
• tumor-associated macrophages
•  tumor cells

Ethics approval

The study was approved by the Local Committee for Medical Ethics of the Cancer Research Institute of TNRMC and was performed according to the guidelines of Declaration of Helsinki. Written consent was obtained from each enrolled subject.

Author contributions

MS conceptualized, designed, and supervised the study, interpreted the results, wrote the manuscript, performed and analysed flow cytometry for monocytes. MP performed the isolation of peripheral blood monocytes, RNA extraction and quantitative real-time PCR, interpreted the results, and edited the manuscript. EK performed flow cytometry for CTC and CSC and analysed the results. MZ performed and analysed the molecular BC subtypes definition and immunohistochemical estimation of TAMs. NT enrolled patients for the study and provided clinical information. NC and EC revised the manuscript and provided administrative, technical, and material support.

Declaration of interest

The authors declare that the research was conducted without any commercial or financial ties that could be construed as a potential conflict of interest.

Additional information

Funding

The work was performed on equipment from the Core Facility «Medical genomics», Tomsk NRMC. This study was supported by the Russian Ministry in the topics of fundamental scientific research "Study of ethno-population characteristics and the molecular basis of the formation, progression, and sensitivity to therapy of malignant neoplasms of various localizations" under Grant АААА-А20-120083190037-4.