158P - The inhibitory effects of canstatin on VEGF-A-induced lymphangiogenesis and metastasis in an oral squamous cell carcinoma SCC-VII animal model

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Clinical research
Cancer biology
Presenter Mun Gyeong Bae
Citation Annals of Oncology (2016) 27 (suppl_9): ix46-ix51. 10.1093/annonc/mdw579
Authors J. Hwang-Bo, M.G. Bae, J. Park, I.S. Chung
  • Department Of Genetic Engineering And Graduate School Of Biotechnology, Kyung Hee University, 17104 - Yongin/KR

Abstract

Background

A spreading of tumor cells to lymph nodes through a lymphangiogenesis is common and an early event in malignant tumor, especially in metastasis of head and neck squamous cell carcinoma (SCC). The inhibition of tumor-induced lymphangiogenesis is a attractive target for therapeutics designed to restrict the metastatic spread of tumor. We investigated the inhibitory effects of canstatin on oral SCC-induced lymphangiogenesis and metastasis both in vivo and in vitro.

Methods

We established an orthotropic oral SCC animal model to investigate the in vivo inhibitory effect of canstatin and analyzed using immunohistochemistry and H&E staining. To examine the inhibitory effect of canstatin on VEGF-A-induced lymphangiognensis, we performed an in vivo Matrigel plug assay. Proliferation, tube formation and migration assay using human lymphatic endothelial cells were also performed. The anti-lymphangiogenic mechanism of canstatin was investigated in lymphatic endothelial cells stimulated by VEGF-A using RT-PCR and western blot analysis.

Results

Canstatin treatment decreased final tumor volumes and weights, as well as densities of blood and lymphatic vessels in an orthotropic oral SCC animal model. Lung metastasis of oral SCC was significantly reduced in canstatin-treated animals. Canstatin reduced VEGF-A expression in SCC-VII cells treated with the hypoxia mimetic agent, CoCl2. VEGF-A induced in vivo lymphatic vessel formation in a Matrigel plug, but this was remarkably reduced in a canstatin-treated Matrigel. Canstatin suppressed the expression of vascular endothelial growth factor receptor (VEGFR)-1 and -2 stimulated by VEGF-A. And canstatin significantly reduced the expression of VEGF-A, VEGFR-1, and -2 in SCC-VII-induced tumors. In addition, canstatin suppressed the VEGF-A-induced phosphorylation of VEGFR-1 and -2.

Conclusions

Our results indicate that canstatin exhibits anti-tumoral and anti-lymphangiogenic activities against oral SCC cells. Anti-lymphangiogenic signaling by canstatin is probably mediated by the suppression of the integrin αvβ3/VEGFR-1 and/or -2 signaling induced by VEGF-A.

Clinical trial indentification

Legal entity responsible for the study

Kyung Hee University

Funding

Basic Science Research Program through the National Research Foundation of Korea (NRF), The Ministry of Education, Science and Technology (NRF-2013R1A1A2062398)

Disclosure

All authors have declared no conflicts of interest.