Related Experiment Videos
[A fragment of collagen XVIII inhibits angiogenesis]
U K Zätterström1, N Fukai, B R Olsen
1Harvard Medical School, Department of Cell Biology, 240 Longwood Ave, Boston, MA 02115, USA.
Background:
Malignant tumours may produce substances with both stimulatory and inhibitory effect on angiogenesis.
Material And Methods:
A protein fragment with angiogenesis-inhibiting potential was recently identified in conditioned media from a murine endothelial tumour cell line.
Results:
The angiogenesis inhibitor, endostatin, is a 20 kDa C-terminal fragment of collagen XVIII, a proteoglycan/collagen found in vessel walls and basement membranes. The generation of endostatin or endostatin-like collagen XVIII fragments is catalyzed by proteolytic enzymes, including cathepsin L and matrix metalloproteases, that cleave peptide bonds within the protease-sensitive hinge region of the C-terminal domain.
Interpretation:
The physiological processing of collagen XVIII to endostatin may represent a local control mechanism for the regulation of angiogenesis. The outcome of ongoing clinical trials will determine the role of endostatin as a possible angiogenesis-inhibiting drug in the future.
Insights
Malignant tumors can release substances that affect blood vessel growth. Researchers identified endostatin, a protein fragment that inhibits angiogenesis, which may be a new cancer treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Context:
- Malignant tumors can influence angiogenesis through secreted factors.
- A novel protein fragment with anti-angiogenic properties was isolated from a murine endothelial tumor cell line.
- Understanding tumor-derived factors is crucial for cancer research.
Purpose:
- To investigate the nature and origin of an angiogenesis-inhibiting protein fragment.
- To characterize endostatin as a C-terminal fragment of collagen XVIII.
- To explore the potential of endostatin as an anti-angiogenic therapeutic agent.
Summary:
- Endostatin, a 20 kDa fragment of collagen XVIII, inhibits angiogenesis.
- Collagen XVIII is a proteoglycan/collagen in vessel walls and basement membranes.
- Proteolytic enzymes like cathepsin L and matrix metalloproteases generate endostatin by cleaving collagen XVIII.
Impact:
- The physiological generation of endostatin from collagen XVIII may be a natural mechanism to control angiogenesis.
- Ongoing clinical trials will ascertain endostatin's efficacy as an angiogenesis-inhibiting drug.
- This research contributes to the development of novel cancer therapies targeting angiogenesis.