Intrinsic differences in cisplatin sensitivity of head and neck cancer celllines correlates to lysosomal pH

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Nilsson, Cathrine,1978-Linköpings universitet,Experimentell patologi,Hälsouniversitetet (author)

Intrinsic differences in cisplatin sensitivity of head and neck cancer celllines correlates to lysosomal pH

Article/chapterEnglish2010

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2009-12-22
John Wiley & Sons,2010
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LIBRIS-ID:oai:DiVA.org:liu-15136
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-15136URI
https://doi.org/10.1002/hed.21317DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:121244547URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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The previous status of this article was Manuscript and the working title was Radiation and cisplatin sensitivity in head and neck cancer cells with stem cell properties.
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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
apoptosis
cathepsin
chemotherapy resistance
lysosome
V0V1-ATPase
Cell biology
Cellbiologi

Added entries (persons, corporate bodies, meetings, titles ...)

Roberg, KarinÖstergötlands Läns Landsting,Linköpings universitet,Oto-Rhino-Laryngologi,Hälsouniversitetet,Öronkliniken US(Swepub:liu)karro26 (author)
Grafström, Roland C.Karolinska Institutet (author)
Öllinger, KarinÖstergötlands Läns Landsting,Linköpings universitet,Experimentell patologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik(Swepub:liu)karol56 (author)
Linköpings universitetExperimentell patologi (creator_code:org_t)

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In:Head and Neck: John Wiley & Sons32:9, s. 1185-11941043-30741097-0347

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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