title: Two populations of TSPO binding sites in oral cancer SCC-15 cells.
abstract: Oral cancer mortality and morbidity rates remain high. The main inducer of oral cancer is cigarette smoke (CS). Translocator protein 18kDa (TSPO) was shown to play a role in carcinogenesis. We characterized TSPO binding sites in human oral cancer cell line SCC-15 and examined effect of CS on TSPO binding. We exposed SCC-15 human squamous cells to cigarette smoke. [3H]PK 11195 binding results were assessed in cells confluent for one day. To characterize the number of population sites, a custom written Matlab program compared Pearson linear correlation coefficients between all points in the Scatchard plot. Using [3H]PK 11195 as a radio ligand, we found that TSPO binding sites are not uniform, but separated into two sub-populations, one with high affinity (respective Kd and Bmax values of 1.40±0.08nM and 1586±48 fmol/mg protein), another with lower affinity (respective Kd and Bmax values of 61±5nM and 26260±1050 fmol/mg protein). We demonstrate rapid decrease in TSPO binding to the high affinity site induced by exposure to CS; specifically, significant 36% decrease in binding after 30min CS exposure (p<0.05), and 69% decrease after 2h CS exposure (p<0.05). Association between TSPO and CS exposure may contribute to understanding the underlying mechanism of oral carcinogenesis.
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: v.avishai@gmail.com.
authors.forename: Avishai
authors.initials: A
authors.lastname: Gavish
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Krayzler
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion - Israel Institute of Technology, Haifa, Israel. Electronic address: nagler@tx.technion.ac.il.
authors.forename: Rafael
authors.initials: R
authors.lastname: Nagler
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000473:pathology*; D018079:Receptors, GABA / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects
chemical_list: D007546:Isoquinolines; D018079:Receptors, GABA; C499229:TSPO protein, human; C037850:PK 11195
keywords: Cigarette smoke; SCC-15 oral cancer cell line; Translocator protein 18kDa (TSPO); [(3)H]PK 11195