Cluster of differentiation 44- and octamer-binding transcription factor-4-positive stem-like osteosarcoma cells involved in tumor development

Abstract

Abstract. Osteosarcoma (OS) is an aggressive primary bone cancer that usually affects children and young adolescents. Previous studies have demonstrated the implications of a small sub-population of cancer stem cells on treatment failure and tumor recurrence. The present study analyzed the characteristic features of the stem-like cells within the human OS-55 cell line. It was identified that 2.3% of the OS-55 cells were cancer stem-like side population (SP) cells. Following treatment with verapamil, the population of SP cells was reduced to 0.7%. The sphere formation assay revealed that the OS cells were able to rapidly form tumor spheres (also known as sarcospheres). Immunofluorescence analysis identified that the OS-55 cells expressed the cluster of differentiation 44, octamer-binding transcription factor-3/4A and Nanog stem cell surface markers. The results of the present study suggest that, as with other tumors, OS also contains a sub-population of cancer stem-like cells, which may have important implications in cancer diagnosis and treatment. IntroductionOsteosarcoma (OS) is the eighth most common malignancy in children and young adolescents, and accounts for 2.4% of all pediatric malignancies. Following diagnosis, the mean survival rate of patients with OS is less than five years (1,2). In total, ~20% of patients are at the metastatic lung stage at the time of diagnosis. Unsuccessful treatment strategies lead to mortality. Therefore, an understanding of the molecular mechanisms that underlie tumorigenesis is important.Previous studies concerning a number of different cancers have identified the existence of a small sub-population of cancer-initiating cells known as cancer stem cells (CSCs), which exhibit stem cell-like properties and are responsible for tumor metastasis, invasion and chemotherapy resistance (3-8).The existence of CSCs has also been demonstrated in human OS, which possesses characteristic features of stem cells and expresses the octamer-binding transcription factor (Oct)3/4A and Nanog stem cell surface markers (9,10). A noteworthy feature of these cells is their ability to efflux Hoechst 3342 dye and other chemotherapeutic drugs (10), which ultimately results in chemoresistance and tumor recurrence.CSCs can be isolated based upon the expression of stem cell surface markers, such as cluster of differentiation (CD)44 and CD133 (11), or by the Hoechst 33342 dye exclusion technique by fluorescence-activated cell sorting (FACS) (12). With FACS, the cells that exclude Hoechst 33342 dye are named the side population (SP) cells. Another technique is the sphere formation assay, in which individual cancer cells form a spherical colony in a defined serum-free medium (10). In each of these methods, the isolated cancer stem-like cells exhibit resistance to chemotherapy and apoptosis, a high level of self-renewal and a higher level of stem cell surface markers. However, the molecular and signaling pathways involved in these functions are yet to be elucidated. The present study attempted to isolate and ch...

Significance of cyclooxygenase‑2, prostaglandin E2 and CD133 levels in sunitinib‑resistant renal cell carcinoma

“…Cancer stem cells (CSCs) are important for cancer progression (13). CSCs are a small subpopulation of cells that exhibit stem-like properties, which are associated with the initiation, chemoresistance, metastasis and recurrence of cancer (13).…”

“…Cancer stem cells (CSCs) are important for cancer progression (13). CSCs are a small subpopulation of cells that exhibit stem-like properties, which are associated with the initiation, chemoresistance, metastasis and recurrence of cancer (13). CSCs express several specific markers that may facilitate the isolation and identification of CSCs, including cluster of differentiation (CD) 133, which is widely expressed (14).…”