Cancer stem cell heterogeneity and spheroid structures in different tumor cell lines

Abstract

Introduction. High mortality, tumor recurrence, and resistance to therapy remain major challenges in oncology and are largely attributed to the presence of a distinct population of tumor cells known as cancer stem cells. They are resistant to adverse conditions and capable of self-renewal daughter cell generation, differentiation, and epithelial–mesenchymal transition. It remains unclear whether tumors contain a single population of stem cells or multiple heterogeneous populations organized in a hierarchical manner. The purpose of our study was to analyze cancer stem cell heterogeneity by investigating marker expression and the association of these cells with spheroidal structures in several tumor cell lines: glioblastoma U-251 and U-87, cervical cancer SiHa and HeLa, vulvar squamous cell carcinoma A431, and lung adenocarcinoma A549. Materials and methods. Immunocytochemical analysis was performed using antibodies against ALDH1, CD133, and CD34 as cancer stem cell markers. Results. Hierarchies of heterogeneous cancer stem cells were presumably found in the studied tumor cell lines. ALDH1+ and CD34+ predominate in A549 lung adenocarcinoma; CD133 and ALDH1, in U-251 and U-87 glioblastoma cultures; and HeLa and SiHa, in cervical carcinomas. Vulvar squamous cell carcinoma A431 is characterized by the lowest number of cancer stem cells. Clusters of cancer stem cells were found in spheroidal structures, which may correspond to their niches identified in the tumor tissue. Conclusion. Understanding cancer stem cell biology may contribute to the development of new therapeutic approaches. Keywords: cancer stem cells, heterogeneity, hierarchy, plasticity, spheroid structures