Oral cancer, cigarette smoke and mitochondrial 18kDa translocator protein (TSPO) - In vitro, in vivo, salivary analysis.
Oral cancer features high rates of mortality and morbidity, and is in dire need for new approaches. In the present study we analyzed 18 kDa translocator protein (TSPO) expression in oral (tongue) cancer tumors by immunohistochemistry. We also assayed TSPO binding in human tongue cancer cell lines and in the cellular fraction of saliva from tongue cancer patients, heavy cigarette smokers, and non-smoking healthy people as controls. Concurrently, TSPO protein levels, cell viability, mitochondrial membrane potential (Deltapsi(m)), and general protein levels were analyzed. TSPO expression could be significantly enhanced in oral cancer tumors, compared to unaffected adjacent tissue. We also found that five-year survival probability dropped from 65% in patients with TSPO negative tumors to 7% in patients with highly expressed TSPO (p<0.001). TSPO binding capacity was also pronounced in the human oral cancer cell lines SCC-25 and SCC-15 (3133+/-643 fmol/mg protein and 6956+/-549 fmol/mg protein, respectively). Binding decreased by 56% and 72%, in the SCC-25 and SCC-15 cell lines, respectively (p<0.05) following CS exposure in cell culture. In the cellular fraction of saliva of heavy smokers TSPO binding was lower than in non-smokers (by 53%, p<0.05). Also the cellular fraction of saliva exposed to CS in vitro showed decreased TSPO binding compared to unexposed saliva (by 30%, p<0.001). Interestingly, oral cancer patients also displayed significantly lower TSPO binding in the cellular fraction of saliva compared to healthy controls (by 40%, p<0.01). Our results suggest that low TSPO binding found in the cellular fraction of saliva may depend on genetic background as well as result from exposure to CS. We suggest that this may be related to a predisposition for occurrence of oral cancer.
Nagler
Rafael
R
Department of Oral and Maxillofacial Surgery and Laboratory of Oral Biochemistry, Rambam Medical Center and the Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096, Israel. nagler@tx.technion.ac.il
Ben-Izhak
Ofer
O
Savulescu
Dana
D
Krayzler
Ella
E
Akrish
Sharon
S
Leschiner
Svetlana
S
Otradnov
Irina
I
Zeno
Sivan
S
Veenman
Leo
L
Gavish
Moshe
M
D000368:Aged; D016022:Case-Control Studies; D002470:Cell Survival / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D018079:Receptors, GABA / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D012463:Saliva / Q000378:metabolism*; D012907:Smoking; D014407:Tumor Cells, Cultured
D018079:Receptors, GABA; D044786:S-Phase Kinase-Associated Proteins; C499229:TSPO protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27