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


KÖPRÜ C. Z., Cagnan I., AKAR İ., ESENDAĞLI G., KORKUSUZ P., Gunel-Ozcan A.

CYTOTHERAPY, cilt.20, sa.7, ss.930-940, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 20 Sayı: 7
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.jcyt.2018.05.002
  • Dergi Adı: CYTOTHERAPY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.930-940
  • Anahtar Kelimeler: apoptosis, cell-based gene delivery, genetically modified MSCs, GITRL, mesenchymal stromal cell, small cell lung cancer, SIVA, STEM-CELLS, T-CELLS, INDUCED APOPTOSIS, PROTEIN LIGAND, GENE-THERAPY, GITR, EXPRESSION, FAMILY, IMMUNITY, DELIVERY
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Background aims. TNFR 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) express GITR. Because mesenchymal stromal cells (MSCs) may target tumor cells, we aimed to investigate the effect of MSCs carrying GITRL overexpressing plasmid on the proliferation and viability of a GITR - SCLC cell line (SCLC-21H) compared with a GITR SCLC cell line (NCI-H82). Methods. Electroporation was used to transfer pGITRL (GITRL gene 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. Results. Proliferation of NCI-H82 was increased in all types of co-cultures while SCLC-21H cells did not. GITRL expressing MSCs were able to induce cell death of SCLC-21H through the upregulation of SIVA I apoptosis inducing factor. Conclusions. The 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.