Reactome | Collagen type XVIII endostatin release

Collagen type XVIII endostatin release

Stable Identifier

R-HSA-2168923

Type

Reaction [transition]

Species

Homo sapiens

Compartment

extracellular region

ReviewStatus

5/5

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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
15950618	Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases Sorsa, T, Rehn, M, Pihlajaniemi, T, Nyberg, P, Salo, T, Heikkilä, P, Heljasvaara, R, Parikka, M, Luostarinen, J	Exp Cell Res	2005
11119712	Generation and degradation of human endostatin proteins by various proteinases Delaissé, J, Ferreras, M, Felbor, U, Lenhard, T, Olsen, BR	FEBS Lett.	2000