期刊
CELL CYCLE
卷 5, 期 7, 页码 681-685出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.5.7.2615
关键词
caspase-8; integrin-mediated death; beta 1 integrins; metastasis; neuroblastoma
类别
资金
- NCI NIH HHS [CA67938, CA21765, CA107263] Funding Source: Medline
Neuroblastoma, a common tumor of nervous system origin in young children, is usually detected only after the primary tumor has metastasized and the chances of its complete removal are low. Metastatic neuroblastoma cells commonly suppress expression of the gene encoding caspase-8. In a neuroblastoma murine model, expression of caspase-8 and integrin alpha 3 beta 1 was dramatically reduced during tumor development. Analysis of clinical biopsies supported the observation that expression of both genes is low in human patients with metastatic disease. These data suggest that loss of expression of both caspase-8 and unligated integrins contribute to the survival of tumor cells migrating from the primary tumor. Integrin receptors that are unable to find appropriate ligands can form a large molecular complex containing caspase-8, explaining why cells that have diminished expression of either of these two genes have a significant survival advantage in foreign microenvironments. Thus, upregulating expression of caspase-8 and integrins, or alternatively, antagonizing integrins within the primary tumor may be important therapeutically in halting neuroblastoma metastasis.
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