Silencing of heparanase by siRNA inhibits tumor metastasis and angiogenesis of human breast cancer in vitro and in vivo.
Expression of the heparanase gene is associated with invasive, angiogenic and metastatic potential of diverse malignant tumors and cell lines. Here we used RNA interference strategies to evaluate the role of human heparanase in breast malignancy and to explore the therapeutic potential of its specific targeting. The siRNA targeting human heparanase almost completely inhibited the expression of heparanase in human breast carcinoma MDA-MB-435 cells, whereas the mismatched siRNA showed no effect. Cells transfected with heparanase siRNA expressed significantly less heparanase and profoundly reduced invasion and adhesion in vitro. In MDA-MB-435 cell xenograft model, tumors treated with siRNA were less vascularized and less metastatic than those treated with saline and the mismatched controls. The association of reduced levels of heparanase and altered tumorigenic properties in cells with anti-heparanase siRNA indicates that heparanase is important in cancer progress and has potential use as a target for anticancer drug development.
Zhang
Zhong-Hua
ZH
Division of Molecular Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Chen
Yi
Y
Zhao
Hua-Jun
HJ
Xie
Cheng-Ying
CY
Ding
Jian
J
Hou
Yong-Tai
YT
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000201:enzymology; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays; D000099175:Heparanase
D005966:Glucuronidase; D034741:RNA, Small Interfering; D000099175:Heparanase