KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state
| Autor: | Dong Hyun Jo, Cheong Whan Chae, Sang Eun Lee, Yoo Wook Kwon, Cheol Lee, Jin Woo Lee, Younghyun Kim, Young Eun Choi, Heeyoung Seok, Jin A. Kang, Sung Hee Baek, Injoo Hwang, Hur Jin, Ji Yeon Yun, Hyo-Soo Kim, Jae Il Choi, Byong Seung Cho |
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| Rok vydání: | 2021 |
| Předmět: |
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Vascular Endothelial Growth Factor A Cancer Research Angiogenesis Neovascularization Physiologic Kangai-1 Protein KAI1 (CD82) Membrane Microdomains Anti-angiogenesis Palmitoylation In vivo medicine Animals Diseases of the blood and blood-forming organs Receptor Molecular Biology RC254-282 Pericyte Mice Knockout Neovascularization Pathologic biology Chemistry Research Neoplasms. Tumors. Oncology. Including cancer and carcinogens Hematology Cell biology Mice Inbred C57BL medicine.anatomical_structure Oncology Endogenous angiogenic growth factor inhibitor Knockout mouse biology.protein Female RC633-647.5 Platelet-derived growth factor receptor Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Hematology & Oncology, Vol 14, Iss 1, Pp 1-21 (2021) Journal of Hematology & Oncology |
| ISSN: | 1756-8722 |
| Popis: | Background Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance. Methods Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo. Results KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo. Conclusions KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors. |
| Databáze: | OpenAIRE |
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