期刊
CANCER SCIENCE
卷 103, 期 7, 页码 1259-1266出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1349-7006.2012.02301.x
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资金
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology (MEST), Republic of Korea [2011-0017639]
- Global Core Research Center (GCRC) from NRF [2011-0035681]
- MEST, Republic of Korea
- National Institutes of Health [R01 CA100816]
- Converging Research Center Program from MEST, Republic of Korea [2011-K000975]
- National Research Foundation of Korea [2011-0017639] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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. (Cancer Sci 2012; 103: 12591266)
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