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Tumor-promoting phorbol esters induce angiogenesis in vivo
P B Morris1, T Hida, P J Blackshear
1Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
The American Journal of Physiology
|February 1, 1988
Summary
Tumor promoters called phorbol esters stimulate new blood vessel growth (angiogenesis) in vivo. This suggests that phorbol esters may support tumor growth by promoting neovascularization, potentially via protein kinase C activation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tumor growth is linked to the development of its vascular supply.
- Phorbol esters are known tumor promoters that activate protein kinase C.
- The precise mechanisms of phorbol ester tumor promotion remain unclear.
Purpose of the Study:
- To investigate whether tumor-promoting phorbol esters can induce vascular growth.
- To determine the role of protein kinase C activation in phorbol ester-induced angiogenesis.
Main Methods:
- Assessing angiogenesis in vivo using the chick chorioallantoic membrane assay.
- Evaluating angiogenesis in vivo using the rabbit cornea assay.
- Testing the mitogenic effects of phorbol esters on bovine capillary endothelial cells in culture.
Main Results:
- Active tumor promoters 12-O-tetradecanoyl phorbol-13-acetate and phorbol 12,13-didecanoate stimulated angiogenesis in a dose-dependent manner.
- 4 alpha-phorbol 12,13-didecanoate, inactive in tumor promotion and protein kinase C activation, did not stimulate angiogenesis.
- No direct mitogenic effect of phorbol esters on endothelial cells in culture was observed, suggesting an indirect angiogenic role.
Conclusions:
- Tumor-promoting phorbol esters stimulate angiogenesis in vivo.
- The tumor-promoting activity of phorbol esters may be partly due to their ability to induce neovascularization.
- Protein kinase C activation appears to play a role in phorbol ester-induced angiogenesis.