Mesenchymal stem cells (MSCs) transplantation has been used for therapeutic applications in various diseases. Here we report MSCs can malignantly transform in vivo. The novel neoplasm was found on the tail of female rat after injection with male rat bone marrow-derived MSCs (rBM-MSCs) and the new tumor cell line, K3, was isolated from the neoplasm. The K3 cells expressed surface antigens and pluripotent genes similar to those of rBM-MSCs and presented tumor cell features. Moreover, the K3 cells contained side population cells (SP) like cancer stem cells (CSCs), which might contribute to K3 heterogeneity and tumorigenic capacity. To investigate the metastatic potential of K3 cells, we established the nude mouse models of liver and lung metastases and isolated the corresponding metastatic cell lines K3-F4 and K3-B6. Both K3-F4 and K3-B6 cell lines with higher metastatic potential acquired more mesenchymal and stemness-related features. Epithelial-mesenchymal transition is a potential mechanism of K3-F4 and K3-B6 formation.

Background: CD123-targeted chimeric antigen receptor (CAR) T cell (CART123) for the treatment of acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm has exhibited potential in clinical trials. However, capillary leakage syndrome, which is associated with endothelial cells damage, is under intensive focus in CART123 therapy. Purpose: The present study aimed to explore the change in CD123 in endothelial cells and the injury to endothelial cells caused by CART123. Methods: The expression of CD123 and cytotoxicity were assessed by flow cytometry. Cytokine release was assessed by ELISA. An in vitro co-culture model was designed to mimic the status, wherein CART123 was stimulated and cytokines were released. Results: In the current study, CART123 exhibited cytotoxicity and the effects of cytokine production on endothelium, and the upregulation of CD123 enhanced the cytotoxicity. The addition of interferon (IFN)-γ and tumor necrosis factor (TNF)-α neutralizing antibodies can effectively reverse the upregulation of CD123 on the endothelial cells caused by CART123, while the cytotoxicity of CART123 in AML cell lines was not affected in vitro. Second, we proved that CD123 expresses in CART123 and would be upregulated after activation, putatively causing an overactivated and fratricide effect. Conclusion: In summary, this study identified that the expression of CD123 on endothelial cells could be upregulated when co-cultured with CART123. Furthermore, IFN-γ and TNF-α could aggravate endothelial damage caused by CART123 in vitro.

There are three most important mismatch repair genes in the mismatch repair system, MSH6 is one of them and it plays an essential role in DNA mismatch repair. Several emerging cell- or animal-based studies have verified that MSH6 mutations are closely linked to the occurrence, progression or metastasis of cancer, but there is still no practicable pan-cancer analysis. On account of the available datasets of the cancer genome atlas (TCGA) and Gene expression omnibus (GEO), a comprehensive analysis of the potential carcinogenic effects of the MSH6 gene was conducted in 33 human cancers. MSH6 was highly expressed in most cancers, and the high expression of MSH6 was associated with poor overall survival prognosis of patients with multiple cancers, such as adrenocortical carcinoma. MSH6 mutations occurred in most cancers and were closely related to the prognosis of cancer patients. Increased phosphorylation levels of S227 and S830 were noted in several tumors, including breast cancer and colon cancer. MSH6 expression was also observed to be correlated with cancer-associated fibroblasts and CD8+ T-cells infiltration levels in various cancer types, e. g. pancreatic adenocarcinoma or testicular germ cell tumors. Furthermore, pathway enrichment analysis demonstrated that the main biological activities of MSH6 were related to ATPase activity, mismatch repair, and DNA metabolism-related functions. Altogether, our pan-cancer research has suggested that the MSH6 expression level was closely related to the carcinogenesis and prognosis of certain tumors, which helps to know the effect of MSH6 in tumorigenesis from the point of view of clinical tumor samples.