[PDF][PDF] Proapoptotic activation of death receptor 5 on tumor endothelial cells disrupts the vasculature and reduces tumor growth

NS Wilson, A Yang, B Yang, S Couto, H Stern… - Cancer cell, 2012 - cell.com
NS Wilson, A Yang, B Yang, S Couto, H Stern, A Gogineni, R Pitti, S Marsters, RM Weimer
Cancer cell, 2012cell.com
The proapoptotic death receptor DR5 has been studied extensively in cancer cells, but its
action in the tumor microenvironment is not well defined. Here, we uncover a role for DR5
signaling in tumor endothelial cells (ECs). We detected DR5 expression in ECs within
tumors but not normal tissues. Treatment of tumor-bearing mice with an oligomeric form of
the DR5 ligand Apo2L/TRAIL induced apoptosis in tumor ECs, collapsing blood vessels and
reducing tumor growth: Vascular disruption and antitumor activity required DR5 expression …
Summary
The proapoptotic death receptor DR5 has been studied extensively in cancer cells, but its action in the tumor microenvironment is not well defined. Here, we uncover a role for DR5 signaling in tumor endothelial cells (ECs). We detected DR5 expression in ECs within tumors but not normal tissues. Treatment of tumor-bearing mice with an oligomeric form of the DR5 ligand Apo2L/TRAIL induced apoptosis in tumor ECs, collapsing blood vessels and reducing tumor growth: Vascular disruption and antitumor activity required DR5 expression on tumor ECs but not malignant cells. These results establish a therapeutic paradigm for proapoptotic receptor agonists as selective tumor vascular disruption agents, providing an alternative, perhaps complementary, strategy to their use as activators of apoptosis in malignant cells.
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