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Intrinsic differences in cisplatin sensitivity of head and neck cancer cell lines: Correlation to lysosomal pH

✍ Scribed by Cathrine Nilsson; Karin Roberg; Roland C. Grafström; Karin Öllinger

Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
390 KB
Volume
32
Category
Article
ISSN
1043-3074

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✦ Synopsis

Abstract

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.

Conclusion

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. © 2009 Wiley Periodicals, Inc. Head Neck, 2010

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