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Insulin-like growth factor binding protein-3 suppresses vascular endothelial growth factor expression and tumor angiogenesis in head and neck squamous cell carcinoma

Authors
 Seung-Hyun Oh  ;  Woo-Young Kim  ;  Ok-Hee Lee  ;  Ju-Hee Kang  ;  Jong-Kyu Woo  ;  Jai-Hyun Kim  ;  Bonnie Glisson  ;  Ho-Young Lee 
Citation
 CANCER SCIENCE, Vol.103(7) : 1259-1266, 2012 
Journal Title
CANCER SCIENCE
ISSN
 1347-9032 
Issue Date
2012
MeSH
Adenoviridae/genetics ; Animals ; Carcinoma, Squamous Cell/blood supply* ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/therapy ; Cell Line, Tumor ; Cell Movement ; Cells, Cultured ; Chick Embryo ; Female ; Gene Transfer Techniques ; Genetic Therapy/methods ; Head and Neck Neoplasms/blood supply* ; Head and Neck Neoplasms/pathology* ; Head and Neck Neoplasms/therapy ; Human Umbilical Vein Endothelial Cells/metabolism ; Human Umbilical Vein Endothelial Cells/physiology ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor Binding Protein 3/genetics* ; Insulin-Like Growth Factor Binding Protein 3/metabolism ; Mice ; Mice, Knockout ; Mice, Nude ; Mutation ; Neovascularization, Pathologic/genetics* ; Neovascularization, Pathologic/therapy ; Neovascularization, Physiologic/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Burden ; Vascular Endothelial Growth Factor A/genetics* ; Vascular Endothelial Growth Factor A/metabolism ; Xenograft Model Antitumor Assays
Keywords
Adenoviridae/genetics ; Animals ; Carcinoma, Squamous Cell/blood supply* ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/therapy ; Cell Line, Tumor ; Cell Movement ; Cells, Cultured ; Chick Embryo ; Female ; Gene Transfer Techniques ; Genetic Therapy/methods ; Head and Neck Neoplasms/blood supply* ; Head and Neck Neoplasms/pathology* ; Head and Neck Neoplasms/therapy ; Human Umbilical Vein Endothelial Cells/metabolism ; Human Umbilical Vein Endothelial Cells/physiology ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor Binding Protein 3/genetics* ; Insulin-Like Growth Factor Binding Protein 3/metabolism ; Mice ; Mice, Knockout ; Mice, Nude ; Mutation ; Neovascularization, Pathologic/genetics* ; Neovascularization, Pathologic/therapy ; Neovascularization, Physiologic/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Burden ; Vascular Endothelial Growth Factor A/genetics* ; Vascular Endothelial Growth Factor A/metabolism ; Xenograft Model Antitumor Assays
Abstract
Angiogenesis, the process by which new blood vessels are recruited to existing ones, is essential for tumor development. Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3), which modulates bioavailability of IGF, has been studied for its potential role in angiogenesis during tissue regeneration and cancer development. In this study, we assessed the role of IGFBP-3 in tumor angiogenesis in head and neck squamous cell carcinoma (HNSCC) and human umbilical vein endothelial cells (HUVECs) using adenoviral (Ad-BP3) and recombinant (rBP3) IGFBP-3. Using an in vivo orthotopic tongue tumor model, we confirmed that both Ad-BP3 and rBP3 suppress the growth of UMSCC38 HNSCC cells in vivo. Ad-BP3 inhibited vascularization in tongue tumors and chorio-allantoic membrane, and suppressed angiogenesis-stimulating activities in UMSCC38 cells. In HUVECs, Ad-BP3 decreased migration, invasion, and tube formation. rBP3 also suppressed production of vascular endothelial growth factor (VEGF) in HUVECs and UMSCC38 cells. IGFBP-3-GGG, a mutant IGFBP-3 with loss of IGF binding capacity, suppressed VEGF production. In addition, we found that IGFBP-3 suppressed VEGF expression, even in mouse embryonic fibroblasts from an IGF-1R-null mouse. Finally, we demonstrated that IGFBP-3-GGG inhibits tumor angiogenesis and growth to the same degree as wild-type IGFBP-3. Taken together, these results support the hypothesis that IGFBP-3 has anti-angiogenic activity in HNSCC, at least in part due to IGF-independent suppression of VEGF production from vascular endothelial cells and cancer cells.
Files in This Item:
T201205748.pdf Download
DOI
22494072
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
Yonsei Authors
Lee, Ok Hee(이옥희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89882
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