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Intrinsic differenc...
Intrinsic differences in cisplatin sensitivity of head and neck cancer celllines correlates to lysosomal pH
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- Nilsson, Cathrine, 1978- (författare)
- Linköpings universitet,Experimentell patologi,Hälsouniversitetet
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- Roberg, Karin (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Oto-Rhino-Laryngologi,Hälsouniversitetet,Öronkliniken US
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- Grafström, Roland C. (författare)
- Karolinska Institutet
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- Öllinger, Karin (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Experimentell patologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik
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(creator_code:org_t)
- 2009-12-22
- 2010
- Engelska.
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Ingår i: Head and Neck. - : John Wiley & Sons. - 1043-3074 .- 1097-0347. ; 32:9, s. 1185-1194
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Cisplatin is part of the treatment regime of head and neck squamous cell carcinomas (HNSCC). In order to predict the clinical outcome of the treatment, markers for evaluation of the intrinsic cisplatin sensitivity are inquired. In this study we characterize the lysosomal compartment and compare cisplatin sensitivity in five HNSCC lines and normal oral keratinocytes (NOKs). Cisplatin sensitivity differed 3-fold between the least and most sensitive cell lines, and the cisplatin LD50 correlated significantly to lysosomal pH, which varied from 4.3 in NOKs to 4.9 in the most resistant HNSCC line. Lysosomes are acidified by the V0V1-ATPase complex located in the lysosomal membrane. Interestingly, in cell lines exhibiting high lysosomal pH, we found decreased expression of the V0V1-ATPase B2 subunit, possibly explaining the defective acidification. In all cell lines, exposure to cisplatin caused activation of caspase-3. Cisplatin exposure was accompanied by lysosomal membrane permeabilization and inhibition of the llysosomal cathepsins B, D and L partly prevented cell death. No correlation between cisplatin sensitivity and expression of cathepsins B, D and L or secretion of their respective proforms into the culture medium was found in the cell lines studied. We conclude that lysosomal pH and expression of V0V1-ATPase subunits are possible future markers of intrinsic cisplatin sensitivity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- apoptosis
- cathepsin
- chemotherapy resistance
- lysosome
- V0V1-ATPase
- Cell biology
- Cellbiologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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