Metastasis suppressor function of tumor necrosis factor-related apoptosis-inducing ligand-R in mice: implications for TRAIL-based therapy in humans?
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapy, as it can induce apoptosis specifically in tumor cells but not in normal cells. Although earlier mouse tumor studies revealed a strong tissue dependency of TRAIL and its death receptor in suppressing primary tumorigenesis or experimental metastases, we recently found that TRAIL-R inhibits lymph node metastases without affecting primary tumor formation in a mouse model of multistage skin tumorigenesis. This finding uncouples the role of TRAIL in primary tumorigenesis from metastasis formation, likely by sensitization of previously TRAIL-resistant tumor cells upon detachment, an early step required for metastasis formation. Therefore, TRAIL-R is a novel metastasis suppressor, suggesting that TRAIL-related tumor therapy might be most effective in primary tumors and early metastatic cancers, before selection for TRAIL resistance occurs.
Grosse-Wilde
Anne
A
Department of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. agwilde@systemsbiology.org
Kemp
Christopher J
CJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*
D000970:Antineoplastic Agents; D053221:TNF-Related Apoptosis-Inducing Ligand