N-/C-terminal deleted mutant of human endostatin efficiently acts as an anti-angiogenic and anti-tumorigenic agent

Heeyeong Cho, Woo Jean Kim, You Mie Lee, Young Mi Kim, Young Guen Kwon, Yong Suk Park, Eu Yul Choi, Kyu Won Kim

Research output: Contribution to journalArticle

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Abstract

Non-collagenous (NC-1) fragments at the C-terminus of basement membrane collagen IV, XV and XIII have been implicated as negative regulators of angiogenesis. Endostatin is an endogenous carboxyl-terminal fragment of collagen XVIII/NC-1, suppressing endothelial cell proliferation, migration in vitro and tumor growth in mouse models. Endostatin can bind zinc through N- and C-terminal residues. Here we demonstrate that N-/C-terminal deleted derivative of human endostatin, H5, effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVECs). Also, tube formation in vitro was comparably inhibited either by H5 or endostatin. The anti-angiogenic and anti-tumorigenic activities of H5 and endostatin were confirmed by an in vivo assay using chick chorioallantoic membrane (CAM) and mouse models, respectively. Treatment of 30 ng of H5 inhibited the capillary formation in CAM by 50%. In addition, H5 exhibited more potent anti-tumor activity than wild-type endostatin in in vivo mouse metastasis assay. These results indicate that the N-/C-terminal deletion mutant would be a strong candidate of anti-cancer agent against spontaneous tumor development and growth.

Original languageEnglish (US)
Pages (from-to)191-195
Number of pages5
JournalOncology Reports
Volume11
Issue number1
StatePublished - Jan 1 2004

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Endostatins
Chorioallantoic Membrane
Neoplasms
Collagen Type XVIII
Human Umbilical Vein Endothelial Cells
Growth and Development
Basement Membrane
Cell Movement
Zinc
Collagen
Endothelial Cells
Cell Proliferation
Neoplasm Metastasis
Growth

Keywords

  • Angiogenesis
  • Endostatin
  • Metastasis

Cite this

Cho, H., Kim, W. J., Lee, Y. M., Kim, Y. M., Kwon, Y. G., Park, Y. S., ... Kim, K. W. (2004). N-/C-terminal deleted mutant of human endostatin efficiently acts as an anti-angiogenic and anti-tumorigenic agent. Oncology Reports, 11(1), 191-195.

N-/C-terminal deleted mutant of human endostatin efficiently acts as an anti-angiogenic and anti-tumorigenic agent. / Cho, Heeyeong; Kim, Woo Jean; Lee, You Mie; Kim, Young Mi; Kwon, Young Guen; Park, Yong Suk; Choi, Eu Yul; Kim, Kyu Won.

In: Oncology Reports, Vol. 11, No. 1, 01.01.2004, p. 191-195.

Research output: Contribution to journalArticle

Cho, H, Kim, WJ, Lee, YM, Kim, YM, Kwon, YG, Park, YS, Choi, EY & Kim, KW 2004, 'N-/C-terminal deleted mutant of human endostatin efficiently acts as an anti-angiogenic and anti-tumorigenic agent', Oncology Reports, vol. 11, no. 1, pp. 191-195.
Cho, Heeyeong ; Kim, Woo Jean ; Lee, You Mie ; Kim, Young Mi ; Kwon, Young Guen ; Park, Yong Suk ; Choi, Eu Yul ; Kim, Kyu Won. / N-/C-terminal deleted mutant of human endostatin efficiently acts as an anti-angiogenic and anti-tumorigenic agent. In: Oncology Reports. 2004 ; Vol. 11, No. 1. pp. 191-195.
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