Isthmin is a novel secreted angiogenesis inhibitor that inhibits tumour growth in mice.
Bottom Line: It encodes a secreted 60 kD protein containing a thrombospondin type 1 repeat domain in the central region and an adhesion-associated domain in MUC4 and other proteins (AMOP) domain at the C-terminal.ISM binds to αvβ(5) integrin on EC surface and supports EC adhesion.Knockdown of isthmin in zebrafish embryos using morpholino antisense oligonucleotides led to disorganized intersegmental vessels in the trunk.
Affiliation: Department of Biological Sciences, National University of Singapore, Singapore.Show MeSH
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Mentions: Although ISM seems to suppress the early stages of EC capillary network formation on Matrigel, neither ISM nor its truncated fragments had any effect on EC attachment to gelatin-, fibronectin- or diluted Matrigel-coated surface (Fig. 5A and data not shown). Similarly, ISM also did not influence EC spreading on these matrix molecules (Fig. S9). On the other hand, ECs can attach and spread onto ISM-coated surface in a similar fashion compared to gelatin-coated surface (Fig. 5B). Furthermore, ISM-C but not ISM-N could support this attachment and spreading (Fig. 5B). These attachment results are in line with results of Fig. 2 above which indicated that only ISM-C inhibited EC capillary network formation similar to full-length ISM. It therefore seems that ISM interacts with ECs through its C-terminal AMOP domain and that ISM most likely interacts with EC surface molecules distinct from receptors for gelatin, fibronectin or the major component of Matrigel such as laminin and collagen IV.
Affiliation: Department of Biological Sciences, National University of Singapore, Singapore.