Inhibition of human angiogenesis with heparin and hydrocortisone

被引:35
作者
Jung S.P. [1 ,2 ]
Siegrist B. [1 ]
Wade M.R. [3 ]
Anthony C.T. [1 ]
Woltering E.A. [1 ,4 ,5 ,6 ]
机构
[1] Departments of Surgery, Louisiana State University, Health Sciences Center, New Orleans, LA
[2] Department of Surgery, Soonchunhyang University, Seoul
[3] Public Health and Biostatistics, New Orleans, LA
[4] Stanley S. Scott Cancer Center, New Orleans, LA
[5] Neurosciences Center of Excellence, New Orleans, LA
[6] Veterans Administration Medical Center, New Orleans, LA
关键词
Angiogenesis; Endothelium; Heparin; Human; Steroids;
D O I
10.1023/A:1014089706107
中图分类号
学科分类号
摘要
Angiogenesis is a critical determinant of tumor growth and the development of metastases. Heparin, steroids, and heparin/steroid combinations have been used in a variety of in vitro models and in vivo in animal models as effective inhibitors of angiogenesis. We tested heparin, steroid and heparin/steroid combinations at a variety of concentrations to determine their effect on the human 'angiogenic switch' from a resting to a proliferative endothelium in vessels from three placentas (initiation), and the effect of these compounds on the subsequent growth of a human angiogenic response (promotion). Using full-thickness human placental vein discs cultured in three-dimensional fibrin-thrombin clots, we demonstrated that heparin (300, 3000 μg/ml), steroid (350, 3500 μg/ml), and combinations of heparin/steroid at these doses effectively blocked both initiation and promotion of a human angiogenic response in a dose-dependent fashion. We also demonstrated that high-dose steroid or heparin/steroid treatment for 15 days resulted in disruption of vessel integrity, while treatment with heparin alone produced a suppressed growth rate but had intact vessel architecture. High-dose heparin/steroid treatment could also disrupt a developed angiogenic response and retard further development of an angiogenic response following the cessation of treatment.
引用
收藏
页码:175 / 185
页数:10
相关论文
共 20 条
[1]  
Algire G., Chalkley H., Legallais F., Park H., Vascular reactions of normal, malignant tumors in vivo. 1. Vascular reactions of mice to wounds and to normal and neoplastic transplants, J Natl Cancer Inst, 6, pp. 73-85, (1945)
[2]  
Tannock I., The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumor, Br J Cancer, 22, pp. 258-273, (1968)
[3]  
Folkman J., Anti-angiogenesis: New concept for therapy of solid tumors, Ann Surg, 175, pp. 409-416, (1972)
[4]  
Brown R., Weiss J., Neovascularization and its role in the osteoarthritic process, Ann Rheum Dis, 47, pp. 881-885, (1988)
[5]  
Waltman D., Gitter K., Yannuzzi L., Schatz H., Choroidal neovascularization associated with choroidal nevi, Am J Ophthalmol, 85, pp. 704-710, (1978)
[6]  
Gartner S., Henkind P., Neovascularization of the iris (rubeosis Iridis), Surv Ophthalmol, 22, pp. 291-312, (1978)
[7]  
Moses M., Langer R., Inhibitors of angiogenesis, Biotechnology, 9, pp. 630-634, (1991)
[8]  
Hobson B., Denekamp J., Endothelial proliferation in tumors and normal tissues continuous labeling studies, Br J Cancer, 49, pp. 405-413, (1984)
[9]  
Folkman J., Langer R., Linhardt R., Et al., Angiogenesis inhibition and tumor regression caused by heparin or a heparin fragment in the presence of cortisone, Science, 221, pp. 719-725, (1983)
[10]  
Folkman J., Weisz P., Joullie' M., Et al., Control of angiogenesis with synthetic heparin substitutes, Science, 243, pp. 1490-1493, (1989)