CXCR4 EXPRESSION IN DIFFERENT SUBSETS OF CTCs AND SINGLE (DETACHED) BREAST CANCER CELLS

O E Savelieva,L A Tashireva,M V Zavyalova,M A Buldakov,E V Denisov,E V Kaigorodova,V M Perelmuter,R H Mukhamedzhanov

doi:10.21294/1814-4861-2018-17-4-75-80

Abstract

The aim of this study was to assess CXCR4 expression in different subsets of CTCs and single (detached) breast cancer cells.Materials and methods. Thirty five patients with invasive breast carcinoma of no specialtype (IC NST) (T1-4N0-2M0), between 29 and 69 years of age were included in this study. Different subsets of CTCs with CXCR4 expression were evaluated by flow cytometry. A confocal microscopy was used to assess CXCR4 expression in different subsets of single (detached) cancer cells in breast tissue.Results. The CXCR4 was expressed in CTCs without stem-like and EMT phenotype, in CTCs with EMT but not stem markers and in stem-like CTCs without EMT features. In all blood samples, the CXCR4 expression in CTCs with stem-like and EMT phenotype was absent. In breast tumor the CXCR4 was expressed in the non stemlike single (detached) breast cancer cells with EMT features, in the single (detached) breast cancer cells with stem and EMT features. In all tumor samples the stem-like or non stem-like single (detached) breast cancer cells without EMT features were absent.Conclusions. Different subsets of the CTCs exhibited CXCR4. The CXCR4 expression did not depend on the presence or absence of stem or/and EMT features in tumor cells. We showed that some subsets of single (detached) breast cancer cells in the primary tumor were characterized by the ability to express CXCR4 and may be a source of the respective CTC subsets.

Highlights

Circulating tumor cells (CTCs) mediate tumor dissemination and play the key role in the metastatic cascade [1, 2]
We showed that some subsets of single breast cancer cells in the primary tumor were characterized by the ability to express CXCR4 and may be a source of the respective CTC subsets
As CXCR4 promotes breast cancer metastasis to distant organs where its ligand, SDF-1, is generated in large quantity [10, 11], we examined the expression of these molecules in different subsets of CTCs in the blood of breast cancer patients (Figure 1)

Summary

Introduction

Circulating tumor cells (CTCs) mediate tumor dissemination and play the key role in the metastatic cascade [1, 2]. Metastasis of cancer cells to distant locations needs intravasation from the primary tumor sites into blood vessels, survival in the circulation, migration to secondary organs, adhesion, and proliferation of cancer cells in targeting organs and tissues [5]. The CXCR4/ CXCL12 axis makes breast cancer cells move out of the circulation and traffic into organs with high amounts of chemokines, and forming metastases [6, 7]. In present study we investigated the CXCR4 expression in different subsets of CTCs and single (detached) breast cancer cells in primary tumor. Material and Methods Patients (n=35) with invasive breast carcinoma of no special type (IC NST) (T1-4N0-2M0) within the range of 29 - 69 years of age (mean age: 49.06 ± 9.78) were treated at the Cancer Research Institute, Tomsk NRMC (Tomsk, Russia) between 2011 and 2017 included (Table 1). This study was approved by the institutional review board, all patients signed an informed consent for voluntary participation

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Conclusion