Metastasis suppressor function of tumor necrosis factor-related apoptosis-inducing ligand-R in mice: implications for TRAIL-based therapy in humans?

Publication Type:

Journal Article

Source:

Cancer research, Volume 68, Issue 15, p.6035-7 (2008)

Keywords:

2008, Animals, Antineoplastic Agents, Center-Authored Paper, Comparative Medicine Core Facility, Experimental Histopathology Core Facility, Human Biology Division, Humans, MICE, Neoplasm Metastasis, Shared Resources, Specialized Pathology Core Facility, TNF-Related Apoptosis-Inducing Ligand

Abstract:

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.