Inhibitors Block Tumors Through Faulty Blood Vessels
May be useful for cancer treatment
THURSDAY, Dec. 21 (HealthDay News) -- Inhibitors of Delta-like ligand 4 (Dll4) can curb tumor growth by producing defective blood vessels and such inhibitors may be useful in cancer treatment, according to two studies in the Dec. 21/28 issue of Nature.
In the first study, Gavin Thurston, Ph.D., and colleagues from Regeneron Research Laboratories in Tarrytown, N.Y., introduced a soluble form of Dll4 into tumor cells to block the interaction of Dll4 with its receptor Notch, and found that the tumor grew more slowly and had a higher density of blood vessels. However, the blood vessels were defective and the tumors were hypoxic. The ability of the soluble Dll4 to inhibit tumor growth was confirmed in several mouse tumor models.
In the second study, Minhong Yan, Ph.D., and colleagues from Genentech, Inc. in South San Francisco, Calif., used a neutralizing anti-Dll4 antibody that specifically blocked only the interaction of Notch with Dll4. The antibody increased endothelial cell proliferation and changed their morphology. The antibody also inhibited tumor growth by causing the growth of defective blood vessels.
"Vascular endothelial growth factor-induced Dll4 acts as a negative regulator of tumor angiogenesis; its blockage results in a striking uncoupling of tumor growth from vessel density, presenting a novel therapeutic approach even for tumors resistant to anti-vascular endothelial growth factor therapies," Thurston and colleagues conclude.