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Role of human cripto-1 in tumor angiogenesis
Caterina Bianco1, Luigi Strizzi, Andreas Ebert
1Tumor Growth Factor Section, Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Journal of the National Cancer Institute
|January 20, 2005
Summary
Human cripto-1 (CR-1) promotes cell transformation and cancer cell invasion. This study found CR-1 stimulates angiogenesis, the formation of new blood vessels, which is crucial for tumor growth.
Area of Science:
- Molecular Biology
- Cancer Research
- Angiogenesis
Background:
- Human cripto-1 (CR-1) is known to promote cell transformation, migration, and invasion in epithelial cells.
- The role of CR-1 in angiogenesis, the formation of new blood vessels, remained largely unexplored.
Purpose of the Study:
- To investigate whether human cripto-1 (CR-1) stimulates angiogenesis.
- To determine the role of CR-1 in new blood vessel formation in vitro and in vivo.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were used for in vitro assays measuring proliferation, migration, invasion, and differentiation.
- In vivo angiogenesis was assessed using Matrigel plugs in nude mice and a breast cancer xenograft model.
- A blocking anti-CR-1 monoclonal antibody was employed to elucidate CR-1's specific role.
Main Results:
- CR-1 significantly stimulated HUVEC proliferation, migration, invasion, and differentiation into vascular-like structures.
- Recombinant CR-1 protein induced microvessel formation in vivo, which was significantly inhibited by an anti-CR-1 antibody.
- Tumors derived from CR-1-transfected breast cancer cells exhibited higher microvessel density compared to control tumors.
Conclusions:
- Human cripto-1 (CR-1) plays a significant role in promoting angiogenesis.
- CR-1 is implicated as a key factor in the complex process of new blood vessel formation.