[Frontiers in Bioscience 16, 674-697, January 1, 2011]

Matricryptins derived from collagens and proteoglycans

Sylvie Ricard-Blum, Lionel Ballut

Institut de Biologie et Chimie des Proteines, UMR 5086 CNRS - University Lyon 1, France


1. Abstract
2. Introduction
3. What are matricryptins and matricryptic sites?
3.1. Definition
3.2. Mechanisms of exposure
4. Matricryptins from collagens
4.1. Matricryptins and cryptic sites of collagen I
4.2. Chondrocalcin, the C-propeptide of collagen II
4.3. Matricryptins and cryptic sites of collagen IV
4.4. Vastatin, a matricryptin of collagen VIII
4.5. Restin, a matricryptin of collagen XV
4.6. Matricryptins of collagen XVIII
4.7. Matricryptin of collagen XIX
5. Matricryptins from proteoglycans and glycosaminoglycans
5.1. Endorepellin
5.2. Hyaluronan fragments
5.3. Heparan sulfate oligosaccharides
6. Matricryptin receptors and signaling
6.1. Matricryptins of collagen IV
6.2. Matricryptins of collagen XVIII
6.3. Endorepellin
6.4. Hyaluronan fragments
7. Physio-pathological processes controlled by matricryptins
7.1. Angiogenesis
7.2. Tumor growth and metastasis
7.3. Tissue remodeling and wound healing
7.4. Inflammation
7.5. Autoimmune and inherited diseases
8. Matricryptins, cryptic sites and therapeutics
8.1. Matricryptins as potential drugs
8.2. Cryptic sites as therapeutic targets
8.3. Matricryptins as potential markers of diseases
9. Perspectives
10. Acknowledgements
11. References


Controlled proteolysis of extracellular matrix components releases bioactive fragments or unmasks cryptic sites that play key roles in controlling various physio-pathological processes including angiogenesis, tissue remodeling, wound healing, inflammation, tumor growth, and metastasis. We review here the structure and mechanisms of release of i) the proteolytic fragments (matricryptins) cleaved from collagens, proteoglycans and glycosaminoglycans, and ii) the matricryptic sites existing in these molecules. The cell surface receptors and the signaling pathways they trigger to exert their biological activities is discussed with the major physio-pathological processes they control. Their involvement in autoimmune and inherited diseases is reported. Most matricryptins issued from collagens, proteoglycans and glycosaminoglycans exhibit anti-angiogenic and anti-tumor properties and their use as potential drugs and as potential disease markers is discussed. Perspectives for identifying the common structural features, if any, of the matricryptins and their use in combination with chemotherapy and