CD44+/CD24+-Expressing Cervical Cancer Cells and Radioresistant Cervical Cancer Cells Exhibit Cancer Stem Cell Characteristics

Abstract

Background: Radiation therapy is a mainstay in the treatment of cervical cancer. However, most advanced and metastatic cervical cancers are resistant to radiation therapy because of the presence of cancer stem cells (CSCs). To date, no specific markers were found for cervical CSCs. Methods: The fraction of CD44+/CD24+ cell subpopulation was detected with flow cytometry (FCM). The clonogenicity and radiosensitivity were detected using colony-formation and radiosensitivity assay. Matrigel-transwell invasion assay was used to compare the invading capacity. We compared the tumor formation capacity using Tumor Xenografts. The expressions of apoptosis related factor, epithelial-mesenchymal transition and stem cell markers were detected with real-time polymerase chain reaction and western blot analysis. Results: This study shows that radiation-resistant cervical cancer cells are rich in CD44+/CD24+-expressing cervical cancer cells. Moreover, these 2 cells exhibit the same CSC characteristics, such as increased expression of Bcl-2, survivin, and stem cell markers being more tumorigenic. These cells also showed phenotypic molecular changes that are consistent with epithelial-mesenchymal transition. Conclusion: Our data suggested that CD44+/CD24+-expressing cervical cancer cells may perform an important function in the radioresistance of cervical cancer. The therapy, which focuses on CD44+/CD24+-expressing cervical cancer cells, can increase the radiosensitivity of cervical cancer.