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Hodgkin-Reed-Sternberg cells inhibit apoptosis via caspase-3 interference

06-16-2006

According to recent research from Germany, Hodgkin-Reed-Sternberg (HRS) cells inhibit apoptosis via caspase-3 interference.

"In this study, the expression of activated caspase-3 by the tumor cells of classical Hodgkin lymphoma (cHL), the HRS cells, is confirmed. This raises the question why caspase-3 does not kill HRS cells," wrote H. Durkop and colleagues, Charite-Universitatsmedizin.

They wrote, "There are only a few molecules, which are able to directly inhibit caspase-3. One of them is cIAP2. We show that cIAP2 is expressed in the HRS cells in 20 of 23 cHL cases by in situ hybridization.

"Suppression experiments with cIAP2 antisense RNA show that down-regulation of cIAP2 significantly reduces apoptosis resistance in cHL cell lines. cIAP2 overexpression appears to be unique for HRS cells since the tumor cells of non-Hodgkin lymphomas are nearly cIAP2-negative."

"We demonstrate that cIAP2 is inducible by CD30 stimulation in cHL cell lines of T-cell origin and anaplastic large cell lymphoma cell lines, whereas cHL cell lines of B-cell origin constitutively express cIAP2. Inhibition of cIAP2 expression by cIAP2 antisense RNA decreases resistance to apoptosis," reported the authors.

The scientists concluded, "The results indicate that cIAP2 contributes to the apoptosis resistance of HRS cells, mainly by inhibiting effector caspases. According to these findings, a therapeutical application of inhibitors of apoptosis proteins antagonists in cHL appears promising."

Durkop and colleagues published their study in the Journal of Molecular Medicine - Jmm (cIAP2 is highly expressed in Hodgkin-Reed-Sternberg cells and inhibits apoptosis by interfering with constitutively active caspase-3. J Mol Med, 2006;84(2):132-141).

For additional information, contact H. Durkop, Charite-Universitatsmedizin, Institute of Pathology, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany.

Publisher contact information for the Journal of Molecular Medicine - Jmm is: Springer, 233 Spring Street, New York, NY 10013, USA.

Keywords: Berlin, Germany, Antisense Technology, Apoptosis Resistance, Hodgkin-Reed-Sternberg Cells, Hodgkin Lymphoma, cIAP2, Caspase, Proteomics.

This article was prepared by Cancer Gene Therapy Week editors from staff and other reports. Copyright 2006, Cancer Gene Therapy Week via NewsRx.com.