• Open Access

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,

    1. College of Pharmacy, Gachon University, Incheon
    2. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
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    • These authors contributed equally to this work.
  • Woo-Young Kim,

    1. College of Pharmacy, Sookmyung Women's University, Seoul
    2. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
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    • These authors contributed equally to this work.
  • Ok-Hee Lee,

    1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
    Current affiliation:
    1. Severance Integrative Research Institute for Cerebral & Cardiovascular Diseases, Yonsei University Health System, Seoul, Korea
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    • These authors contributed equally to this work.
  • Ju-Hee Kang,

    1. National Cancer Center, Goyang-si, Gyeonggi-do
    2. Department of Food and Nutrition, Chung-Ang University, Ansung, Gyeonggi-do, Korea
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  • Jong-Kyu Woo,

    1. College of Pharmacy, Seoul National University, Seoul, Korea
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  • Jai-Hyun Kim,

    1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
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  • Bonnie Glisson,

    1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
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  • Ho-Young Lee

    Corresponding author
    1. College of Pharmacy, Seoul National University, Seoul, Korea
    • College of Pharmacy, Gachon University, Incheon
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Errata

This article is corrected by:

  1. Errata: Correction Volume 103, Issue 8, 1600, Article first published online: 26 July 2012

To whom correspondence should be addressed.

E-mail: hylee135@snu.ac.kr

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. (Cancer Sci 2012; 103: 1259–1266)

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