Dual Effect of Glucocorticoid-Induced Tumor Necrosis Factor–Related Receptor Ligand Carrying Mesenchymal Stromal Cells on Small Cell Lung Cancer: A Preliminary in vitro Study

摘要

Background aimsTNFR family member glucocorticoid-induced tumor necrosis factor–related receptor (GITR/TNFRSF18) activation by its ligand glucocorticoid-induced TNF-related receptor ligand (GITRL) have important roles in proliferation, death and differentiation of cells. Some types of small cell lung cancers (SCLCs) expressGITR. Because mesenchymal stromal cells (MSCs) may target tumor cells, we aimed to investigate the effect of MSCs carryingGITRLoverexpressing plasmid on the proliferation and viability of a GITR+SCLC cell line (SCLC-21H) compared with a GITR–SCLC cell line (NCI-H82).MethodsElectroporation was used to transfer pGITRL (GITRLgene carrying plasmid) or pCR3 (mock plasmid) into MSCs. Flow cytometry and semi-quantitative polymerase chain reaction were used to characterize the transfected MSCs. Following SCLC-21H or NCI-H82 cell lines were co-cultured with pGITRL-MSCs.ResultsProliferation of NCI-H82 was increased in all types of co-cultures while SCLC-21H cells did not.GITRLexpressing MSCs were able to induce cell death of SCLC-21H through the upregulation ofSIVA1apoptosis inducing factor.ConclusionsThe influence of MSCs on SCLC cells can vary according to the cancer cell subtypes as obtained in SCLC-21H and NCI-H82 and enabling GITR-GITRL interaction can induce cell death of SCLC cell lines.