Gicerin/Cd146 is involved in zebrafish cardiovascular development and tumor angiogenesis

Angiogenesis plays an important role in vertebrate development and tumor growth. In this process, gicerin, which is known as a kind of cell adhesion molecule, has recently been reported to play an important role but its in vivo function is still unclear in developing vasculature. To address this iss...

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Published in:Genes to cells : devoted to molecular & cellular mechanisms 2010-11, Vol.15 (11), p.1099-1110
Main Authors: So, Ju‐Hoon, Hong, Sung‐Kook, Kim, Hyun‐Taek, Jung, Seung‐Hyun, Lee, Mi‐Sun, Choi, Jung‐Hwa, Bae, Young‐Ki, Kudoh, Tetsuhiro, Kim, Ji‐Hun, Kim, Cheol‐Hee
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
Blood Vessels - embryology
Blood Vessels - metabolism
CD146 Antigen - physiology
Danio rerio
Embryo, Nonmammalian - metabolism
Freshwater
Gene Knockdown Techniques
In Situ Hybridization
Microinjections
Neoplasms - blood supply
Neoplasms - metabolism
Neovascularization, Pathologic - metabolism
Neovascularization, Physiologic - physiology
Oligonucleotides, Antisense - administration & dosage
Oligonucleotides, Antisense - pharmacology
Signal Transduction
Vascular Endothelial Growth Factors - metabolism
Zebrafish
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Summary:Angiogenesis plays an important role in vertebrate development and tumor growth. In this process, gicerin, which is known as a kind of cell adhesion molecule, has recently been reported to play an important role but its in vivo function is still unclear in developing vasculature. To address this issue, we used gain‐of‐function and loss‐of‐function analyses of gicerin in zebrafish. In the gain of function experiments using enforced expression of various domains of gicerin constructs, extracellular domain induced angiogenic sprouting defects, most notably in the intersegmental vessels, whereas the cytoplasmic domain of gicerin did not affect angiogenic sprouting. Moreover, morpholino‐mediated knockdown of gicerin in embryos resulted in angiogenic sprouting defects in intersegmental vessels. Mechanistically, the angiogenic function of gicerin was found to be genetically linked to VEGF signaling in the knock‐down experiments using vegf‐a mRNA, VEGFR inhibitor and gicerin morpholino. In addition to the physiological angiogenesis during development, gicerin morphants efficiently blocked the tumor angiogenesis in zebrafish. Thus, knock‐down of gicerin might have an important implication in controlling tumor angiogenesis.
ISSN:1356-9597
1365-2443
DOI:10.1111/j.1365-2443.2010.01448.x