The angiopoietin-like factor cornea-derived transcript 6 is a putative morphogen for human cornea.
The human cornea-specific protein cornea-derived transcript 6 (CDT6) is a member of the angiopoietin gene family. We report the structural and functional characterization of CDT6. We demonstrate that CDT6 is a secreted protein that folds into disulfide-linked homotetramers by coiled-coil interactions. The finding that CDT6 is expressed at high levels in the avascular corneal stromal layer suggested that the protein, similar to certain angiopoietins, acts as a negative regulator of angiogenesis. To test this hypothesis and to assay the effect of the protein on a growing tissue with high vascular density, CDT6 was expressed in a mouse xenograft model. Expression of CDT6 led to a reduction in tumor growth and aberrant blood vessel formation by inducing massive fibrosis. Interestingly, expression of CDT6 also resulted in the deposition of extracellular matrix components typical for the mature corneal stromal layer. These observations strongly suggest a role as morphogen for CDT6 in inducing a corneal phenotype in vivo.
Peek
Ron
R
Department of Molecular Immunology, Netherlands Ophthalmic Research Institute, Amsterdam 1105 BA, The Netherlands. r.peek@ioi.knaw.nl
Kammerer
Richard A
RA
Frank
Sabine
S
Otte-Höller
Irene
I
Westphal
Johan R
JR
D042683:Angiopoietin-1; D000091302:Angiopoietin-Like Protein 2; D000075803:Angiopoietin-Like Protein 4; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D001798:Blood Proteins; D003315:Cornea / Q000737:chemistry*; D005109:Extracellular Matrix / Q000378:metabolism; D005136:Eye Proteins / Q000737:chemistry / Q000502:physiology*; D006023:Glycoproteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008546:Melanoma, Experimental / Q000517:prevention & control; D008562:Membrane Glycoproteins; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009124:Muscle Proteins; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D017433:Protein Structure, Secondary; D014407:Tumor Cells, Cultured
C467630:ANGPT1 protein, human; C485792:ANGPTL2 protein, human; D042683:Angiopoietin-1; D000091302:Angiopoietin-Like Protein 2; D000075803:Angiopoietin-Like Protein 4; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C467628:Angpt1 protein, mouse; C407088:Angptl4 protein, mouse; D001798:Blood Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009124:Muscle Proteins