Radiation Response of Cervical Cancer Stem Cells Is Associated with Pretreatment Proportion of These Cells and Physical Status of HPV DNA

Abstract

Radio- and chemoresistance of cancer stem cells (CSCs) is considered as one of the possible causes of adverse results of chemoradiotherapy for various malignancies, including cervical cancer. However, little is known about quantitative changes in the CSC subpopulation in the course of treatment and mechanisms for individual response of CSCs to therapy. The purpose of the study was to evaluate the association of radiation response of cervical CSCs with clinical and morphological parameters of disease and features of human papillomavirus (HPV) infection. The proportion of CD44+CD24low CSCs was determined by flow cytometry in cervical scrapings from 55 patients with squamous cell carcinoma of uterine cervix before treatment and after fractionated irradiation at a total dose of 10 Gy. Real-time PCR assay was used to evaluate molecular parameters of HPV DNA. Post-radiation increase in the CSC proportion was found in 47.3% of patients. Clinical and morphological parameters (stage, status of lymph node involvement, and histological type) were not significantly correlated with radiation changes in the CSC proportion. Single- and multifactor analyses revealed two independent indicators affecting the radiation response of CSCs: initial proportion of CSCs and physical status of HPV DNA (R = 0.86, p = 0.001 for the multiple regression model in the whole).

The Integration Pattern of Human Papillomavirus in the Host Genome as a Promising Guide for Precise Radiation Therapy in Cervical Cancer

“…In a recent study by Zamulaeva et al (36), radioresistance of CC cells was found to be dependent on both integration of HPV DNA into the host cell genome and amount of this integration. This study demonstrated that the percentage of cancer stem cells (CSCs) increased after irradiation in tumors with fully integrated HPV DNA whereas the proportion of CSCs decreased in tumors with episomal or partly integrated forms.…”

Infection by High-Risk Human Papillomaviruses, Epithelial-to-Mesenchymal Transition and Squamous Pre-Malignant or Malignant Lesions of the Uterine Cervix: A Series of Chained Events?

“…As for physiological EMT, that also accompanies SCC onset or progression occurs gradually, explaining why cells with intermediate phenotypes between the fully epithelial and the decidedly mesenchymal ones can be found in the squamous lesions of the uterine cervix [88][89][90][91][92][93][94][95][96][97]. Such a variety of phenotypes could depend on the multitude of EMT promoters that may be present in the cervix of HPV-infected women, and on the temporal sequence according to which cervical epithelial cells are exposed to these factors.…”

Synthesis and Characterization of Salinomycin-Loaded High-Density Lipoprotein and Its Effects on Cervical Cancer Cells and Cervical Cancer Stem Cells

“…It has been proved that CD44 high CD24 low cervical cancer cells have the characteristics of CSCs. [34][35][36] CCSCs with CD44 high CD24 low were separated from CCCs (HeLa cells) by a magnetic separator. The proportion of CD44 high CD24 low cells in CCSCs was 97.2%, which was much higher than 1.52% in CCCs, indicating that the CD44 high CD24 low subpopulation has been successfully enriched from CCCS (Figure 2A).…”