Angiopoietin-1 Inhibits Vascular Permeability, Angiogenesis, and Growth of Hepatic Colon Cancer Tumors

作者: Oliver Stoeltzing , Niels Reinmuth , Corazon D. Bucana , Jane S. Wey , Wenbiao Liu

DOI:

关键词:

摘要: Angiopoietin (Ang)-1 and -2 are critical regulators of embryonic postnatal neovascularization. Ang-1 activates the endothelial cell-specific tyrosine kinase receptor Tie-2, which in turn leads to enhanced cell survival stabilization. The effects on tumor angiogenesis remain controversial; although we have previously demonstrated that overexpression colon cancer cells a decrease s.c. growth, others shown may be proangiogenic. Few studies addressed role Angs tumors growing organ metastatic growth. We hypothesized inhibit growth cancers liver by inhibition angiogenesis. also wanted investigate mechanisms affects vivo. Human (HT29) were stably transfected with an construct or empty vector (pcDNA) injected directly into livers nude mice. After 37 days, harvested weighed, sizes measured. In additional experiment, validate paracrine effect Ang-1, various mixtures control Ang-1-transfected livers, was assessed. Direct recombinant studied vivo Gelfoam assay. impact vascular permeability investigated using intradermal Miles assay conditioned media from cells. Liver weights (P < 0.05), volumes vessel counts 0.01), proliferation 0.01) group significantly lower than those group. Tumor vessels developed higher degree pericyte coverage 0.02) pcDNA tumors. mixture even as few 1:10 cells/control resulted significant reduction hepatic 0.04). assay, implants decreased addition 0.01). Finally, medium more 0.05). Our results suggest is important regulator this secondary increasing periendothelial support Thus, could potentially serve antineoplastic anti-permeability agent for patients colorectal cancer.

参考文章(43)
Folkman J, The role of angiogenesis in tumor growth. Seminars in Cancer Biology. ,vol. 3, pp. 65- 71 ,(1992)
Michael J. Hansbury, Roberto F. Nicosia, Wen-Hui Zhu, Steven J. Holmes, James D. Winkler, Production and characterization of a Tie2 agonist monoclonal antibody. Angiogenesis. ,vol. 4, pp. 29- 36 ,(2001) , 10.1023/A:1016678828930
Parth S. Ray, Tatiana Estrada-Hernandez, Hiroaki Sasaki, Li Zhu, Nilanjana Maulik, Early effects of hypoxia/reoxygenation on VEGF, Ang-1, Ang-2 and their receptors in the rat myocardium: Implications for myocardial angiogenesis Molecular and Cellular Biochemistry. ,vol. 213, pp. 145- 153 ,(2000) , 10.1023/A:1007180518474
Isaiah J. Fidler, Angiogenesis and cancer metastasis. Cancer Journal. ,vol. 6, pp. 20- ,(2000)
Syed A. Ahmad, Wenbiao Liu, Young D. Jung, Fan Fan, Niels Reinmuth, Corazon D. Bucana, Lee M. Ellis, Differential expression of angiopoietin-1 and angiopoietin-2 in colon carcinoma. A possible mechanism for the initiation of angiogenesis. Cancer. ,vol. 92, pp. 1138- 1143 ,(2001) , 10.1002/1097-0142(20010901)92:5<1138::AID-CNCR1431>3.0.CO;2-L
A J Hayes, W-Q Huang, J Yu, P C Maisonpierre, A Liu, F G Kern, M E Lippman, S W McLeskey, L-Y Li, Expression and function of angiopoietin-1 in breast cancer British Journal of Cancer. ,vol. 83, pp. 1154- 1160 ,(2000) , 10.1054/BJOC.2000.1437
Corazon D. Bucana, Yasuhiko Kitadai, Karen R. Cleary, Lee M. Ellis, Yutaka Takahashi, Expression of Vascular Endothelial Growth Factor and Its Receptor, KDR, Correlates with Vascularity, Metastasis, and Proliferation of Human Colon Cancer Cancer Research. ,vol. 55, pp. 3964- 3968 ,(1995)
Gavin Thurston, John S. Rudge, Ella Ioffe, Hao Zhou, Leorah Ross, Susan D. Croll, Nicole Glazer, Jocelyn Holash, Donald M. McDonald, George D. Yancopoulos, Angiopoietin-1 protects the adult vasculature against plasma leakage. Nature Medicine. ,vol. 6, pp. 460- 463 ,(2000) , 10.1038/74725
R M Shaheen, S A Ahmad, W Liu, N Reinmuth, Y D Jung, W W Tseng, K E Drazan, C D Bucana, D J Hicklin, L M Ellis, Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors British Journal of Cancer. ,vol. 85, pp. 584- 589 ,(2001) , 10.1054/BJOC.2001.1936
Christiane J. Bruns, Wenbiao Liu, Darren W. Davis, Raymond M. Shaheen, David J. McConkey, Michael R. Wilson, Corazon D. Bucana, Daniel J. Hicklin, Lee M. Ellis, Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases Cancer. ,vol. 89, pp. 488- 499 ,(2000) , 10.1002/1097-0142(20000801)89:3<488::AID-CNCR3>3.0.CO;2-X