Open AccessInsulin‐like growth factor binding protein‐3 suppresses vascular endothelial growth factor expression and tumor angiogenesis in head and neck squamous cell carcinoma
Author(s) -
Oh SeungHyun,
Kim WooYoung,
Lee OkHee,
Kang JuHee,
Woo JongKyu,
Kim JaiHyun,
Glisson Bonnie,
Lee HoYoung
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02301.x
Subject(s) - angiogenesis , vascular endothelial growth factor , head and neck squamous cell carcinoma , cancer research , growth factor , insulin like growth factor binding protein , biology , vascular endothelial growth factor a , cancer , endocrinology , medicine , insulin like growth factor , head and neck cancer , receptor , vegf receptors
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 ( HUVEC s) using adenoviral (Ad‐BP3) and recombinant ( rBP 3) IGFBP‐3. Using an in vivo orthotopic tongue tumor model, we confirmed that both Ad‐BP3 and rBP 3 suppress the growth of UMSCC 38 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. rBP 3 also suppressed production of vascular endothelial growth factor ( VEGF ) in HUVEC s and UMSCC 38 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. ( Cancer Sci 2012; 103: 1259–1266)