CXC Chemokine Ligand 16 Promotes the Proliferation and Migration of Hodgkin and Reed-Sternberg Cells Via the PI3K/Akt/NF-κB Signaling Pathway

Abstract

Hodgkin’s Lymphoma (HL) is a main type of lymphoma characterized by Hodgkin’s Reed-Sternberg(H/RS) cells, which involves in many cytokines and chemokines. CXC Chemokine Ligand 16 (CXCL16) was reported to be expressed in various cancer types and was previously observed by our group to highly express in H/RS cells, yet the function and mechanism of CXCL16, as well as soluble CXCL16 (sCXCL16) on the phenotypes of HRS cells needs to be fully elucidated. To investigate the effects of CXCL16 on cell proliferation, migration, cell cycle, apoptosis, and immune-phenotypes of H/RS cells, an H/RS cell line (L428) transfected with CXCL16-overexpressed lentivirus vector was established and identified; besides, recombinant sCXCL16 was also applied on L428 cell lines in the present study. Results showed that both endogenously overexpressed CXCL16 and exogenously applied recombinant sCXCL16 protein were able to promote the proliferation and migration of L428 cells, and diminished cell apoptosis, while the immune phenotypes of L428 cells showed no significant changes. Blocking the interaction between the ligand CXCL16 and its unique receptor CXCR6 with antibody suppressed the above effects. As the pathways involved were concerned, results showed that CXCL16 upregulated the expression of several phosphorylated proteins of the PI3K/Akt and NF-κB signaling pathways, which were markedly inhibited by PI3K inhibitor LY294002 or CXCR6 antibody. The present study suggests that CXCL16 promotes the proliferation and migration of H/RS cell through its receptor CXCR6. The mechanism may involve activation of the PI3K/Akt/NF-κB signaling pathways.