title: The MOC31PE immunotoxin reduces cell migration and induces gene expression and cell death in ovarian cancer cells.
abstract: BACKGROUND
  The standard treatment of ovarian cancer with chemotherapy often leads to drug resistance and relapse of the disease, and the need for development of novel therapy alternatives is obvious. The MOC31PE immunotoxin binds to the cell surface antigen EpCAM, which is expressed by the majority of epithelial cancers including ovarian carcinomas, and we studied the cytotoxic effects of MOC31PE in ovarian cancer cells.
  
  
  METHODS
  Investigation of the effects of MOC31PE treatment on protein synthesis, cell viability, proliferation and gene expression of the ovarian cancer cell lines B76 and HOC7.
  
  
  RESULTS
  MOC31PE treatment for 24 h caused a dose-dependent reduction of protein synthesis with ID50 values of less than 10 ng/ml, followed by reduced cell viability. In a gene expression array monitoring the expression of 84 key genes in cancer pathways, 13 of the genes were differentially expressed by MOC31PE treatment in comparison to untreated cells. By combining MOC31PE and the immune suppressor cyclosporin A (CsA) the MOC31PE effect on protein synthesis inhibition and cell viability increased tenfold. Cell migration was also reduced, both in the individual MOC31PE and CsA treatment, but even more when combining MOC31PE and CsA. In tumor metastasis PCR arrays, 23 of 84 genes were differentially expressed comparing CsA versus MOC31PE + CsA treatment. Increased expression of the tumor suppressor KISS1 and the nuclear receptor NR4A3 was observed, and the differential candidate gene expression was confirmed in complementary qPCR analyses. For NR4A3 this was not accompanied by increased protein expression. However, a subcellular fractionation assay revealed increased mitochondrial NR4A3 in MOC31PE treated cells, suggesting a role for this protein in MOC31PE-induced apoptotic cell death.
  
  
  CONCLUSIONS
  The present study demonstrates that MOC31PE may become a new targeted therapy for ovarian cancer and that the MOC31PE anti-cancer effect is potentiated by CsA.
authors: Merete Thune
authors: MT
authors: Wiiger
authors: Hemaseh
authors: H
authors: Bideli
authors: Oystein
authors: O
authors: Fodstad
authors: Kjersti
authors: K
authors: Flatmark
authors: Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. yvonne.andersson@rr-research.no.
authors: Yvonne
authors: Y
authors: Andersson
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D000922:Immunotoxins / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D059648:Kisspeptins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011987:Receptors, Steroid / Q000096:biosynthesis / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D018796:Immunoconjugates; D000922:Immunotoxins; C106628:KISS1 protein, human; D059648:Kisspeptins; C000602279:MOC31PE immunotoxin; C490412:NR4A3 protein, human; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D016572:Cyclosporine