Cancer Stem Cells and Somatic Stem Cells as Potential New Drug Targets, Prognosis Markers, and Therapy Efficacy Predictors in Breast Cancer Treatment

Olga Pershina,Darius Widera,Alexander Dygai,Elena Slonimskaya,Natalia Ermakova,Mariia Zhukova,Edgar Pan,Sergey G Morozov,Evgenii G Skurikhin,Angelina Pakhomova,Aslan Kubatiev

doi:10.3390/biomedicines9091223

Abstract

New drug targets, markers of disease prognosis, and more efficient treatment options are an unmet clinical need in breast cancer (BC). We have conducted a pilot study including patients with luminal B stage breast cancer IIA–IIIB. The presence and frequency of various populations of cancer stem cells (CSC) and somatic stem cells were assessed in the blood, breast tumor tissue, and normal breast tissue. Our results suggest that patients with BC can be divided into two distinct groups based on the frequency of aldehyde dehydrogenase positive cells (ALDH1+ cells) in the blood (ALDH1hi and ALDH1low). In the ALDH1hi cells group, the tumor is dominated by epithelial tumor cells CD44+CD24low, CD326+CD44+CD24−, and CD326−CD49f+, while in the ALDH1low cells group, CSCs of mesenchymal origin and epithelial tumor cells (CD227+CD44+CD24− and CD44+CD24−CD49f+) are predominant. In vitro CSCs of the ALDH1low cells group expressing CD326 showed high resistance to cytostatics, CD227+ CSCs of the ALDH1hi cells group are sensitive to cytostatics. Epithelial precursors of a healthy mammary gland were revealed in normal breast tissue of patients with BC from both groups. The cells were associated with a positive effect of chemotherapy and remission in BC patients. Thus, dynamic control of their presence in blood and assessment of the sensitivity of CSCs to cytostatics in vitro can improve the effectiveness of chemotherapy in BC.

Highlights

IntroductionDespite advances in diagnosis and treatment, breast cancer (BC) remains the leading cause of cancer death in women [1]
When studying blood samples from patients with breast cancer (BC), we found an increase in the number of tumor cells with overexpression of CD227 and CD326, as well as cancer stem cells (CSC) of mesenchymal origin (CD44+ CD24− ) compared to the levels in healthy volunteers (Figure 4)
In BC an increase in the number of ALDH1+ cells circulating in the blood was observed

Summary

Introduction

Despite advances in diagnosis and treatment, breast cancer (BC) remains the leading cause of cancer death in women [1]. More than 1 million new cases of the disease are registered annually [2]. After the diagnosis of BC, prognosis of complications and the choice of optimal drug therapy are crucial [3]. Traditional prognostic measures are the definition of metastases in the lymph nodes, the size of the tumor, and the type of differentiation of tumor cells [1,3]. When searching for tumor markers, much attention is paid to the tumor subtype, which is determined by the presence (or absence) of the estrogen receptor (ER), progesterone receptor (PR), and the protein associated with the Biomedicines 2021, 9, 1223.

Methods

Results

Conclusion