No abstract

Human osteosarcoma is a common primary malignancy of the bone in children and adolescents. It has been reported that curcumin is able to induce apoptosis in osteosarcoma MG63 cells through the mitochondrial pathway. However, whether curcumin is able to induce autophagy and the interaction between apoptosis and autophagy in osteosarcoma cells has yet to be fully elucidated. In the current study, it was determined that curcumin was able to significantly induce apoptosis, and lead to autophagy in MG63 cells. Notably, inhibition of apoptosis enhanced curcumin-induced autophagy due to upregulation of the c-Jun N-terminal kinase (JNK) signaling pathway. This finding was confirmed by the use of JNK-specific inhibitor, SP600125. Furthermore, our data showed that curcumin-induced apoptosis was increased when autophagy was completely inhibited by 3-methyladenine in MG63 cells. These results suggest that autophagy may have an important role in resistance to apoptosis when MG63 cells are incubated with curcumin. Thus, these results provide important insights into the interaction between apoptosis and autophagy in osteosarcoma cells and clinical treatment strategies using curcumin.

No abstract

Spinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are involved in tumor progression is still unknown. Here, our single-cell RNA-sequencing analyses of three spinal ependymoma subtypes dissect the microenvironmental landscape of spinal ependymomas and reveal tumor-associated macrophage (TAM) subsets with distinct functional phenotypes. CCL2+ TAMs are related to the immune response and exhibit a high capacity for apoptosis, while CD44+ TAMs are associated with tumor angiogenesis. By combining these results with those of single-cell ATAC-sequencing data analysis, we reveal that TEAD1 and EGR3 play roles in regulating the functional diversity of TAMs. We further identify diverse characteristics of both malignant cells and TAMs that might underlie the different malignant degrees of each subtype. Finally, assessment of cell-cell interactions reveal that stromal cells act as extracellular factors that mediate TAM diversity. Overall, our results reveal dual functions of TAMs in tumor progression, providing valuable insights for TAM-targeting immunotherapy.