title: Immune escape of AKT overexpressing ovarian cancer cells.
abstract: Platinum-resistance is the most crucial problem for treatment of ovarian cancer. There is a clinical need for new treatment strategies which overcome platinum resistance. As survival is strongly influenced by immunological parameters, immunotherapeutic strategies appear promising. Therefore a better understanding of the interaction between ovarian tumour cells and cells of the immune system is a necessary prerequisite. In the present study we aimed to enlighten the interactions between platinum resistant and platinum sensitive ovarian cancer cells and natural-killer (NK)-cells. Modified FATAL assay was used for determining the killing efficiency of NK-cells for the parental A2780 cells and the cis-platinum resistant A2780cis human ovarian cancer cells. Expression of pro- and anti-apoptotic genes as well as ligands involved in NK-cell receptor recognition were analysed by RT-PCR and flow cytometric analysis. The efficiency of NK mediated cell lysis differs between A2780 cells and the cis-platinum-resistant A2780cis cells. A2780cis cells are less accessible for NK-cell mediated killing. Based on this observation we characterized the molecular basis for resistance mechanisms. Besides an increase in anti-apoptotic genes (especially CIAP-1 and -2) that probably render A2780cis cells more resistant against apoptosis an increased amount of soluble MICA/B seems to be responsible for the lower killing rate of platinum-resistant A2780cis cells compared to their parental A2780 cells.
authors: Department of Gynecology, University Hospital of Würzburg, D-97080 Würzburg, Germany.
authors: Jens C
authors: JC
authors: Hahne
authors: Susanne R
authors: SR
authors: Meyer
authors: Stepan
authors: S
authors: Gambaryan
authors: Ulrich
authors: U
authors: Walter
authors: Johannes
authors: J
authors: Dietl
authors: Jörg B
authors: JB
authors: Engel
authors: Arnd
authors: A
authors: Honig
mesh_terms: D017209:Apoptosis; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000276:immunology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D010984:Platinum / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D010984:Platinum; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt