Endogenous angiogenesis inhibitor vasohibin1 exhibits broad-spectrum antilymphangiogenic activity and suppresses lymph node metastasis.
During cancer progression, the angiogenesis that occurs is involved in tumor growth and hematogenous-distant metastasis, whereas lymphangiogenesis is involved in regional lymph node metastasis. Angiogenesis is counterregulated by various endogenous inhibitors; however, little is known about endogenous inhibitors of lymphangiogenesis. We recently isolated vasohibin1 as an angiogenesis inhibitor intrinsic to the endothelium and further demonstrated its anticancer activity through angiogenesis inhibition. Here, we examined the effect of vasohibin1 on lymphangiogenesis. Vasohibin1 exhibited broad-spectrum antilymphangiogenic activity in the mouse cornea induced by factors including VEGF-A, VEGF-C, FGF2, and PDGF-BB. We then inoculated highly lymph node-metastatic cancer cells into mice and examined the effect of vasohibin1 on lymph node metastasis. Tail-vein injection of adenovirus containing the human vasohibin1 gene inhibited tumor lymphangiogenesis and regional lymph node metastasis. Moreover, local injection of recombinant vasohibin1 inhibited lymph node metastasis. These results suggest vasohibin1 to be the first known intrinsic factor having broad-spectrum antilymphangiogenic activity and indicate that it suppresses lymph node metastasis.
Heishi
Takahiro
T
Department of Vascular Biology, Institute of Development, Tohoku University, Aoba-ku, Sendai 980-8575, Japan.
Hosaka
Tomoko
T
Suzuki
Yasuhiro
Y
Miyashita
Hiroki
H
Oike
Yuichi
Y
Takahashi
Takashi
T
Nakamura
Takumi
T
Arioka
Shingo
S
Mitsuda
Yuichi
Y
Takakura
Tomoaki
T
Hojo
Kanji
K
Matsumoto
Mitsunobu
M
Yamauchi
Chihiro
C
Ohta
Hideki
H
Sonoda
Hikaru
H
Sato
Yasufumi
Y
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D011994:Recombinant Proteins / Q000737:chemistry
D020533:Angiogenesis Inhibitors; D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; C493181:VASH1 protein, human; C510089:Vash1 protein, mouse