Soluble PTK7 inhibits tube formation, migration, and invasion of endothelial cells and angiogenesis.
Human PTK7 is a defective receptor protein tyrosine kinase and its expression is upregulated in various cancers including colorectal carcinomas. To determine whether PTK7 functions in angiogenesis, we have expressed and purified the extracellular domain of PTK7 (soluble PTK7; sPTK7) as a decoy receptor to counteract the effects of endogenous PTK7. Capillary-like tube formation of human umbilical vascular endothelial cells (HUVECs) was accompanied by modulation in the PTK7 mRNA level. Neutralization of endogenous PTK7 with sPTK7 inhibited vascular endothelial growth factor (VEGF)-induced tube formation, migration, and invasion of HUVECs in a dose-dependent manner. sPTK7 reduced VEGF-induced phosphorylation of focal adhesion kinase (FAK) and paxillin, relocalization of paxillin to focal adhesions, and formation of stress fibers. Moreover, sPTK7 inhibited VEGF-induced angiogenesis in vivo. Knockdown of PTK7 using siRNA also inhibited VEGF-induced tube formation, supporting that sPTK7 specifically blocks function of the endogenous PTK7. These results demonstrate that PTK7 plays an important role not only in tube formation, migration, and invasion of endothelial cells but also in angiogenesis.
Shin
Won-Sik
WS
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
Maeng
Yong-Sun
YS
Jung
Jae-Won
JW
Min
Jeong-Ki
JK
Kwon
Young-Guen
YG
Lee
Seung-Taek
ST
D000818:Animals; D002196:Capillaries / Q000254:growth & development; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement; D016764:Cell Polarity / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D022502:Stress Fibers / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D051419:Paxillin; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C096905:PTK7 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human