title: Uptake and phototoxicity of meso-tetrahydroxyphenyl chlorine are highly  variable in human biliary tract cancer cell lines and correlate with markers of  differentiation and proliferation.
abstract: Photodynamic therapy (PDT) using Photofrin and, recently, Foscan has gained broad acceptance for palliative treatment of non-resectable cholangiocarcinoma (CC). No information, however, is available whether the phenotype of CC tumour cells has an effect on the efficiency of the treatment. Using a well-characterised set of n = 9 biliary tract cancer cell lines this study investigated the uptake, phototoxicity, and release of meso-tetrahydroxyphenyl chlorine (mTHPC, Foscan) after incubation with 200 or 400 ng ml(-1) mTHPC. For uptake of mTHPC we found great variations between the individual cell lines (up to a factor 2), resulting in even more pronounced differences in phototoxicity. Based on statistical classification by hierarchical cluster analysis, two groups of cell lines can be distinguished which are characterised by either high or low susceptibility towards mTHPC-based photodynamic treatment. Correlation analysis with previously established immunochemical parameters showed that cells with a low cytokeratin-19 (ductal differentiation), high vimentin (mesenchymal marker), and high proliferative phenotype preferentially show higher uptake of mTHPC and subsequent phototoxicity. These results demonstrate high variability of biliary tract cancer cells when subjected to mTHPC-based photodynamic treatment and identify possible markers that could be used in the clinical setting in order to predict the efficiency of PDT and adjust the dose for complete tumour elimination.
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Muellner Hauptstrasse 48, 5020, Salzburg, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kiesslich
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.forename: Beate
authors.initials: B
authors.lastname: Alinger
authors.forename: Gerhard L
authors.initials: GL
authors.lastname: Jansky
authors.forename: Juergen
authors.initials: J
authors.lastname: Berlanda
authors.forename: Vahagn
authors.initials: V
authors.lastname: Mkrtchyan
authors.forename: Matthias
authors.initials: M
authors.lastname: Ocker
authors.forename: Kristjan
authors.initials: K
authors.lastname: Plaetzer
authors.forename: Frieder
authors.initials: F
authors.lastname: Berr
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity; D001661:Biliary Tract Neoplasms / Q000503:physiopathology*; D014408:Biomarkers, Tumor; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008027:Light; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics* / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009943:Organophosphorus Compounds; C014850:tetramethylolphosphonium chloride