1. Dual targeting of vascular endothelial growth factor and bone morphogenetic protein-9/10 impairs tumor growth through inhibition of angiogenesis.
- Author
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Akatsu Y, Yoshimatsu Y, Tomizawa T, Takahashi K, Katsura A, Miyazono K, and Watabe T
- Subjects
- Activin Receptors, Type II chemistry, Activin Receptors, Type II genetics, Activin Receptors, Type II pharmacology, Activin Receptors, Type II therapeutic use, Animals, Bone Morphogenetic Proteins metabolism, Cell Proliferation, Female, Growth Differentiation Factor 2 antagonists & inhibitors, Growth Differentiation Factor 2 metabolism, Humans, Immunoglobulin Fc Fragments genetics, Immunoglobulin Fc Fragments pharmacology, Immunoglobulin Fc Fragments therapeutic use, Mice, Mice, Inbred BALB C, Mice, Nude, Pancreatic Neoplasms blood supply, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins pharmacology, Recombinant Fusion Proteins therapeutic use, Vascular Endothelial Growth Factor A metabolism, Vascular Endothelial Growth Factor Receptor-1 chemistry, Vascular Endothelial Growth Factor Receptor-1 genetics, Vascular Endothelial Growth Factor Receptor-1 pharmacology, Vascular Endothelial Growth Factor Receptor-1 therapeutic use, Xenograft Model Antitumor Assays, Antineoplastic Combined Chemotherapy Protocols, Bone Morphogenetic Proteins antagonists & inhibitors, Neovascularization, Pathologic drug therapy, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Signal Transduction drug effects, Vascular Endothelial Growth Factor A antagonists & inhibitors
- Abstract
Clinical development of anti-angiogenic agents has been a major landmark in cancer therapy for several types of cancers. Signals mediated by both vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-9 and 10 have been implicated in tumor angiogenesis. However, previous studies have shown that targeting the individual signals was not sufficiently effective in retarding tumor growth in certain preclinical and clinical conditions. In the present study, we developed a novel decoy chimeric receptor that traps both VEGF and BMP-9/10. Single targeting of either VEGF or BMP-9/10 signals significantly reduced the formation of tumor vessels in a mouse xenograft model of human pancreatic cancer; however, it did not show significant therapeutic effects on tumor growth. In contrast, dual targeting of the angiogenic signals resulted in more significant inhibition of tumor angiogenesis, leading to delay of tumor growth. Our findings suggest that simultaneous blockade of VEGF and BMP-9/10 signals is a promising therapeutic strategy for the cancers that are resistant to anti-VEGF and BMP-9/10 therapies., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Published
- 2017
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