Studies on the effect and mechanism of CD147 on melanoma stem cells

Background: Melanoma is the most aggressive form of skin cancer. Melanoma stem cells (MSCs) are one of the driving forces of melanoma invasion and metastasis. Therefore, it is of great significance to explore the mechanisms that maintain the stemness of MSCs. In this study, CD147-positive (CD147+) MSCs derived from A375 cell line were characterized. Methods: Side population (SP) and non-SP cells were sorted from A375 cells. Quantitative real-time polymerase chain reaction and Western blot analysis were conducted to determine the expression of CD147 in SP and non-SP cells. Subsequently, CD147+ and CD147-negative (CD147-) cells were isolated from SP cells. Stem cell characteristics and metastatic potential of CD147+/- antigen-presenting cells were identified by sphere-forming, wound-healing, and transwell assays. Western blot analysis was performed to evaluate the protein levels of transforming growth factor-beta1 (TGFβ1) and neurogenic locus notch homolog protein 1 (Notch1) signaling pathway. Xenograft tumor experiments were conducted to investigate the tumorigenic capacity of CD147+ cells in vivo. Results: CD147 was highly expressed in SP cells of A375 cell line. CD147+ cells have stronger abilities for sphere forming, migration, and invasion in vitro. The protein levels of TGFβ1, notch1, jagged1, and Hes1 were higher in CD147+ cells than in CD147- cells. Moreover, the CD147+ cells showed stronger tumorigenic and metastatic potential in vivo. Conclusion: SP cells of A375 cell line expressed high levels of CD147, and CD147+ SP cells possessed much stronger stem-like characteristics and motility, which is linked to the activation of TGFβ and notch pathways (AU)

Studies on the effect and mechanism of CD147 on melanoma stem cells.

BACKGROUND: Melanoma is the most aggressive form of skin cancer. Melanoma stem cells (MSCs) are one of the driving forces of melanoma invasion and metastasis. Therefore, it is of great significance to explore the mechanisms that maintain the stemness of MSCs. In this study, CD147-positive (CD147+) MSCs derived from A375 cell line were characterized. METHODS: Side population (SP) and non-SP cells were sorted from A375 cells. Quantitative real-time polymerase chain reaction and Western blot analysis were conducted to determine the expression of CD147 in SP and non-SP cells. Subsequently, CD147+ and CD147-negative (CD147-) cells were isolated from SP cells. Stem cell characteristics and metastatic potential of CD147+/- antigen-presenting cells were identified by sphere-forming, wound-healing, and transwell assays. Western blot analysis was performed to evaluate the protein levels of transforming growth factor-beta1 (TGFß1) and neurogenic locus notch homolog protein 1 (Notch1) signaling pathway. Xenograft tumor experiments were conducted to investigate the tumorigenic capacity of CD147+ cells in vivo. RESULTS: CD147 was highly expressed in SP cells of A375 cell line. CD147+ cells have stronger abilities for sphere forming, migration, and invasion in vitro. The protein levels of TGFß1, notch1, jagged1, and Hes1 were higher in CD147+ cells than in CD147- cells. Moreover, the CD147+ cells showed stronger tumorigenic and metastatic potential in vivo. CONCLUSION: SP cells of A375 cell line expressed high levels of CD147, and CD147+ SP cells possessed much stronger stem-like characteristics and motility, which is linked to the activation of TGFß and notch pathways.

Knockdown of BATF3 Inhibits Gastric Cancer Cell Growth and Radioresistance via S1PR1/STAT3 Pathway.

OBJECTIVE: Gastric cancer is one of the most common and deadly cancers worldwide. Basic leucine zipper transcription factor ATF-like 3 (BATF3) plays a key role in tumor immunity. However, the function of BATF3 in gastric cancer remains unclear. Here, we demonstrated BATF3 positively regulated proliferation and radioresistance of gastric cancer cells by regulating S1PR1/STAT3 pathway. METHODS: The RNA-seq analyzed the gene expression by UALCAN web portal and Tumor Immune Estimation Resource. RT-qPCR and western blot was performed to verify BATF3 expression in gastric cancer cells. The assays of CCK-8, EdU incorporation and colony formation were used to analyze cell proliferation, and radioresistance in AGS and MKN45 cells. Flow cytometry was used to detect the cell apoptosis of AGS and MKN45 in treatment with si-BATF3 or radiation. Finally, western blot was performed to measure the expression of cell apoptosis-related modules including Bax, cleaved-caspase3, cleaved-PARP and assess the regulation of S1PR1/STAT3 pathway. RESULTS: BATF3 expression was upregulated in gastric cancer cells. Knockdown of BATF3 suppressed proliferation, radioresistance but promoted the radiation-induced apoptosis of gastric cancer cells through positively regulating S1PR1 expression and STAT3 phosphorylation. CONCLUSIONS: Knockdown of BATF3 inhibits gastric cancer cell growth and radioresistance via S1PR1/STAT3 pathway. BATF3 would become a potential diagnostic indicator for gastric cancer and target of therapeutic treatment.