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

Abstract

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.