Angiopoietin-Like Protein 7 (ANGPTL-7, Cornea-Derived Transcript 6, CDT6)

Angiopoietin-like Protein 7 (ANGPTL-7, Cornea-Derived Transcript 6, CDT6) is a member of the angiopoietin family of structurally related proteins, characterized by a coiled N-terminal domain and a C-terminal fibrinogen like domain. While ANGPTL7 shares the structural features of the angiopoietin family, it plays a critical role in blocking the vascular endothelial Tie2 receptor to which other family members bind. Through the blocking of the Tie2 receptor, ANGPTL7 does not act angiopoietin properties, but rather acts as a morphogen that contributes to the avascularity and transparency of the cornea during both embryo and adult development. Human ANGPTL7 is expressed at high levels in the avascular corneal stromal layer, a site of pathological angiogenesis normally devoid of blood vessels, suggesting that the protein acts as a negative regulator of angiogenesis in a manner similar to that of angiopoietin-1 and angiopoietin-2. In mouse xenograft models, ANGPTL7overexpression has been shown to lead to increased extracellular matrix components typical of a mature corneal stromal layer, as well as the reduction of tumor growth and aberrant blood vessel formation. Overexpression in human melanoma models shows a contradictory, up-regulation of endostatin, an endogenous angiostatic factor, in comparison to the down-regulation observed in mouse models.