Title: 213bi-Induced Death of Hsc45-M2 Gastric Cancer Cells Is Characterized by G2 Arrest and Up-Regulation of Genes Known to Prevent Apoptosis but Induce Necrosis and Mitotic Catastrpophe
Authors: SEIDL C.PORT M.GILBERTZ K.MORGENSTERN ALFREDBRUCHERTSEIFER FRANKSCHWAIGER M.ROEPER B.SENEKOWITSCH-SCHMIDTKE R.ABEND M.
Citation: MOLECULAR CANCER THERAPEUTICS vol. 6 no. 8 p. 2346-2359
Publisher: AMER ASSOC CANCER RESEARCH
Publication Year: 2007
JRC N°: JRC38225
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC38225
Type: Articles in Journals
Abstract: Tumor cells are efficiently killed after incubation with A-emitter immunoconjugates targeting tumor-specific antigens. Therefore, application of A-emitter immunoconjugates is a promising therapeutic option for treatment of carcinomas that are characterized by dissemination of single tumor cells in the peritoneum like ovarian cancer or gastric cancer. In diffuse-type gastric cancer, 10% of patients express mutant d9-E-cadherin on the surface of tumor cells that is targeted by the monoclonal antibody d9MAb. Coupling of the A-emitter 213Bi to d9MAb provides an efficient tool to eliminate HSC45-M2 gastric cancer cells expressing d9-E-cadherin in vitro and in vivo. Elucidation of the molecular mechanisms triggered by A-emitters in tumor cells could help to improve strategies of A-emitter radioimmunotherapy. For that purpose, gene expression of 213Bi-treated tumor cells was quantified using a real time quantitative-PCR low-density array covering 380 genes in combination with analysis of cell proliferation and the mode of cell death. We could show that 213Bi-induced cell death was initiated by G2 arrest;up-regulation of tumor necrosis factor (TNF), SPHK1, STAT5A, p21, MYT1, and SSTR3; and down-regulation of SPP1, CDC25 phosphatases, and of genes involved in chromosome segregation. Together with morphologic changes, these results suggest that 213Bi activates death cascades different from apoptosis. Furthermore, 213Bitriggered up-regulation of SSTR3 could be exploited for improvement of the therapeutic regimen.
JRC Institute:Institute for Transuranium Elements

Files in This Item:
There are no files associated with this item.


Items in repository are protected by copyright, with all rights reserved, unless otherwise indicated.