A novel peptide from human apolipoprotein(a) inhibits angiogenesis and tumor growth by targeting c-Src phosphorylation in VEGF-induced human umbilical endothelial cells.
Many angiogenesis inhibitors are derived from large plasma proteins. Previous studies showed that the Kringle5-like domain (termed KV) in human apolipoprotein (a) is a potential antiangiogenic factor. However, its active region and the underling molecular mechanism remain elusive. Here, we identified an 11-amino acid peptide (named KV11) as the key region for the antiangiogenic function of the KV domain of apolipoprotein (a). We demonstrate that KV11 inhibits angiogenesis in vitro by suppressing human umbilical vein endothelial cell migration and microtubule formation. KV11 inhibits angiogenesis in chicken chorioallantoic membrane assays and mouse corneal micropocket angiogenesis assays in vivo. KV11 peptide shows no effect on tumor cell growth or proliferation, but significantly inhibits tumor growth in SCID mouse xenograft tumor model (p < 0.01) by preventing tumor angiogenesis. We elucidate that KV11 peptide suppresses angiogenesis and tumor progression by targeting the c-Src/ERK signaling pathways. Together, these studies provide the first evidence that KV11 from apolipoprotein KV domain has anti-angiogenesis functions and may be an anti-tumor drug candidate.
Yi
Zheng-Fang
ZF
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Cho
Sung-Gook
SG
Zhao
Hui
H
Wu
Yuan-Yuan
YY
Luo
Jian
J
Li
Dali
D
Yi
Tingfang
T
Xu
Xun
X
Wu
Zirong
Z
Liu
Mingyao
M
D000818:Animals; D001054:Apolipoproteins A / Q000737:chemistry* / Q000494:pharmacology; D053241:Apoprotein(a) / Q000737:chemistry / Q000502:physiology*; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry*; D010766:Phosphorylation; D014471:Umbilical Veins / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
D001054:Apolipoproteins A; C534296:KV11 peptide, human; D010446:Peptide Fragments; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D019061:src-Family Kinases; D053241:Apoprotein(a)