Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin.
Actively growing tumor cells shed membrane vesicles into the extracellular milieu both in vivo and in vitro. Extracellular membrane vesicles from tumor cells contain most surface antigens and proteases present on these cells. They facilitate the escape of tumors from immune surveillance and promote tumor cell invasion. Here, we demonstrate that tumor membrane vesicles stimulate an additional important activity for tumor growth and metastasis by promoting endothelial cell migration, invasion, and tube formation, and inducing in vivo neovascularization. Our data show that tumor vesicles are one of the multiple effectors involved in tumor-induced angiogenesis. Heat-treated vesicles and lipid extracts from the vesicles also induce endothelial cell migration and in vivo angiogenesis. We identify sphingomyelin as the active component for vesicle-induced endothelial cell migration, tube formation, and neovascularization. Together with previously reported results, our data demonstrate that shed tumor vesicles play multiple roles in tumor growth and metastasis by promoting angiogenesis, tumor invasion, and immune escape.
Kim
Chan Woo
CW
Department of Oncology, Graduate School of East-West Medical Science, Kyung Hee University, Yong In, 449-701, Korea.
Lee
Hwan Myung
HM
Lee
Tae Hoon
TH
Kang
Chulhun
C
Kleinman
Hynda K
HK
Gho
Yong Song
YS
D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology*; D005354:Fibrosarcoma / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology; D013109:Sphingomyelins / Q000502:physiology*
D013109:Sphingomyelins