Intrinsic differences in cisplatin sensitivity of head and neck cancer cell lines: Correlation to lysosomal pH.
BACKGROUND
Cisplatin treatment is beneficial for approximately 20% of patients with head and neck squamous cell carcinoma (HNSCC). Tools to predict the clinical outcome and evaluate intrinsic cisplatin sensitivity are, therefore, required.


METHODS
Cisplatin sensitivity, lysosomal pH, and cell death pathway was studied in 5 HNSCC lines and compared with normal oral keratinocytes.


RESULTS
We identified a linear relationship between lysosomal pH and cisplatin sensitivity. Reduced lysosomal acidification was correlated to decreased expression of the V(0)V(1)-ATPase B2 subunit, which is part of the lysosomal acidifying complex. Cisplatin caused apoptosis accompanied by lysosomal membrane permeabilization, and inhibition of lysosomal proteases (cathepsins) partly prevented cell death.


CONCLUSIONS
Cisplatin-induced apoptosis of HNSCC is more efficient in cell lines with low lysosomal pH and is mediated by the release of lysosomal content. Lysosomal pH and expression of V(0)V(1)-ATPase subunits are possible future markers of intrinsic cisplatin sensitivity.
Nilsson
Cathrine
C
Experimental Pathology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. cathrine.nilsson@liu.se
Roberg
Karin
K
Grafström
Roland C
RC
Ollinger
Karin
K
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D002945:Cisplatin