Silencing of S100A4, a metastasis-associated protein, in endothelial cells inhibits tumor angiogenesis and growth.
Endothelial cells express S100A4, a metastasis-associated protein, but its role in angiogenesis remains to be elucidated. Here we show that knockdown of S100A4 in mouse endothelial MSS31 cells by murine specific small interference RNA (mS100A4 siRNA) markedly suppressed capillary-like tube formation in vitro, in early stage after the treatment, along with down- and up-regulation of some of the pro-angiogenic and anti-angiogenic gene expression, respectively. Of particular note is that intra-tumor administration of the mS100A4 siRNA in a human prostate cancer xenograft significantly reduced tumor vascularity and resulted in the inhibition of tumor growth. These findings show that S100A4 in endothelial cells is involved in tube formation, and suggest its potential as a molecular target for inhibiting tumor angiogenesis, which warrants further development of endothelial S100A4-based strategies for cancer treatment.
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Takahiro
T
Ochiya
Keizo
K
Takenaga
Hideya
H
Endo
D000818:Animals; D045744:Cell Line, Tumor; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis* / Q000235:genetics
D009363:Neoplasm Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C077591:S100A4 protein, human