Collagen type XVIII endostatin release

Stable Identifier
R-HSA-2168923
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Collagen type XVIII is a heparan sulfate proteoglycan associated with the basement membranes of almost all epithelia and endothelia. It has a large C-terminal noncollagenous domain. Mouse knockouts suggest that it may have a role in maintaining the structural integrity of the extracellular matrix (Utriainen et al. 2004).

Proteolytic cleavage of the C-terminal noncollagenous domain by matrix metalloproteinases (Heljasvaara et al. 2005) releases 18 to 38 kDa C-terminal proteolytic fragments, collectively named endostatin. They have anti-angiogenic activity (O'Reilly et al. 1997, Ständker et al. 1997) and suppress primary tumor and metastasis growth in experimental animal models (Ortega & Werb 2002). It is not clear whether this collagen subtype forms supramolecular assemblies (Myllyharju & Kivirikko, 2004) but thought likely, via a similar mechanism to the related collagen XV (Hurskainen et al. 2010).

Endostatin-like fragments are released from collagen type XVIII by MMP 7 (Lin et al. 2001), 3, 9, 12, 13 (Ferreras et al. 2000) and 20 (Heljasvaara et al. 2005). Several cathepsins and elastase can bring about endostatin release (Ferreras et al. 2000, Felbor et al. 2000).

Literature References
PubMed ID Title Journal Year
11119712 Generation and degradation of human endostatin proteins by various proteinases

Ferreras, M, Felbor, U, Lenhard, T, Olsen, BR, Delaissé, J

FEBS Lett. 2000
15950618 Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases

Heljasvaara, R, Nyberg, P, Luostarinen, J, Parikka, M, Heikkilä, P, Rehn, M, Sorsa, T, Salo, T, Pihlajaniemi, T

Exp Cell Res 2005
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
serine-type endopeptidase activity of Endostatin-releasing proteases [extracellular region]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created