Role of Cancer Stem-like Cells in the Process of Invasion and Mesenchymal Transformation by a Reconstituted Triple-negative Breast Cancer Cell Population Resistant to P53-induced Apoptosis

Overview

Journal Acta Histochem Cytochem

Specialty Biochemistry

Date 2022 Nov 21

PMID 36405550

Authors

Sana Inoue

Miki Imanishi

Ai Kanzaki

Atsumi Fujimoto

Marina Maeyama

Ayaka Okamoto

Hiroka Matsuda

Kiyotsugu Yoshikawa

Rei Takahashi

Affiliations

Soon will be listed here.

Abstract

We investigated the role of cancer stem cells (CSCs) in a population of triple-negative breast cancer (TNBC) cells that are resistant to apoptosis. A human breast cancer cell population capable of inducing p53 expression with doxycycline (Dox) was created and used as an untreated control (UT). After the addition of Dox to UT for 5 days, the cell population reconstituted with cells showing resistance to apoptosis was named RE. Fluorescence-activated cell sorting (FACS) and immunostaining revealed that after the addition of Dox, the ratio of cells in the S and G2/M phases decreased in UT as apoptosis proceeded, but did not markedly change in apoptosis-resistant RE. CSC-like cells in RE exhibited a cell morphology with a larger ratio of the major/minor axis than UT. FACS showed that RE had a higher proportion of CSC-like cells and contained more CD44CD24 mesenchymal CSCs than ALDH1A3 epithelial-like CSCs. In a Matrigel invasion assay, UT was more likely to form a three-dimensional cell population, whereas RE exhibited a planar population, higher migration ability, and the up-regulated expression of epithelial-mesenchymal transition-related genes. These results provide insights into the mechanisms by which TNBC cells acquire treatment resistance at the time of recurrence.

Citing Articles

Immunolocalization of Cytoplasmic ER in ER-negative Breast Carcinoma as a Potent Favorable Prognostic Predictor.

Ebata A, Suzuki T, Shoji-Harada N, Hamanaka Y, Miyashita M, Iwabuchi E Acta Histochem Cytochem. 2023; 56(4):59-66.

PMID: 37680573 PMC: 10480483. DOI: 10.1267/ahc.23-00016.

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