160P - The inhibitory effects of recombinant canstatin and 3-oacetyloleanolic acid on angiopoietin-1-induced lymphangiogenesis

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Clinical research
Presenter Jeon Hwang-Bo
Citation Annals of Oncology (2016) 27 (suppl_9): ix46-ix51. 10.1093/annonc/mdw579
Authors K.O. Jang, 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

The spread of tumor cells to lymph nodes commonly occurs in tumors and is an early event in metastasis tumor disease. Angiopoietin-1 is a major angiogenic and lymphangiogenic growth factor in colon carcinoma CT-26 cells at a hypoxic condition. In this study, we investigated the inhibitory effects of recombinant canstatin and 3-O-acetyloleanolic acid (3AOA) on angiopoietin-1-induced lymphangiogenesis both in vitro and in vivo.

Methods

To examine the inhibitory effects of recombinant canstatin and 3AOA on angiopoietin-1-induced lymphangiognensis, we performed proliferation, tube formation and migration assay using human lymphatic endothelial cells. The inhibitory effects of recombinant canstatin and 3AOA were further determined in an angiopoietin-1-stimulated in vivo Matrigel plug and a heterotropic CT-26 colon carcinoma animal model. The anti-lymphangiogenic mechanisms of recombinant canstatin and 3AOA were investigated in lymphatic endothelial cells stimulated by angiopoietin-1 using RT-PCR and western blot analysis.

Results

Recombinant canstatin or 3AOA inhibited the proliferation, tube formation, and migration of angiopoietin-1-treated human lymphatic endothelial cells. Recombinant canstatin inhibited lymphangiogenesis via suppression of integrin-dependent FAK signaling induced by angiopoietin-1/Tie-2 and/or VEGFR-3. 3AOA inhibited the activation of signaling factors such as FAK, AKT, and ERK1/2 involved in angiopoietin-1/Tie-2 signaling pathway. Recombinant canstatin and 3AOA reduced the development of new lymphatic vessels in angiopoietin-1-stimulated Matrigel plug. Also recombinant canstatin and 3AOA inhibited the tumor growth and tumor-induced lymphangiogenesis in heterotropic CT-26 colon carcinoma animal model.

Conclusions

Our results indicate that recombinant canstatin and 3AOA exhibit anti-lymphangiogenic effects on angiopoietin-1-induced lymphangiogenesis. Our findings suggest that recombinant canstatin and 3AOA have a potential to inhibit colon carcinoma. Currently, we investigate the combinatory effects of recombinant canstatin and 3AOA.

Legal entity responsible for the study

Kyung Hee University

Funding

Basic Science Research Program through the National Research Foundation of Korea (NRF), Ministry of Education, Science and Technology (NRF-2015R1D1A1A01059824)

Disclosure

All authors have declared no conflicts of interest.