Dual targeting of vascular endothelial growth factor and bone morphogenetic protein‐9/10 impairs tumor growth through inhibition of angiogenesis
| Autor: | Yuichi Akatsu, Tetsuro Watabe, Kazuki Takahashi, Yasuhiro Yoshimatsu, Kohei Miyazono, Akihiro Katsura, Taishi Tomizawa |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A Cancer Research Angiogenesis Activin Receptors Type II Recombinant Fusion Proteins Mice Nude ALK1 Vascular endothelial growth inhibitor Bone morphogenetic protein 03 medical and health sciences chemistry.chemical_compound angiogenesis Mice 0302 clinical medicine Pancreatic cancer Report Antineoplastic Combined Chemotherapy Protocols medicine Growth Differentiation Factor 2 Animals Humans Receptor Cell Proliferation Mice Inbred BALB C Vascular Endothelial Growth Factor Receptor-1 vascular endothelial growth factor Neovascularization Pathologic business.industry BMP‐9/10 General Medicine medicine.disease Xenograft Model Antitumor Assays Blockade Immunoglobulin Fc Fragments Vascular endothelial growth factor Fc‐chimera Pancreatic Neoplasms 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Immunology Bone Morphogenetic Proteins Cancer research Female Decoy business Signal Transduction |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 1347-9032 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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