title: The potential of osteopontin as a therapeutic target for human colorectal cancer.
abstract: OBJECTIVE
  Osteopontin (OPN), a phosphorylated glycoprotein, is involved in tumor progression and metastasis. Previously, we have reported that high OPN mRNA expression level possessed clinicopathological or prognostic significance in human colorectal cancer (CRC). The aim of this study is to investigate whether OPN can serve as a novel molecular target for CRC therapy.
  
  
  METHODS
  Western Blot assay was performed to detect the expression of OPN protein in 18 CRC and corresponding nontumor colon tissue samples. RNA interference (RNAi) was employed to knockdown endogenous OPN expression in CRC cell line (LoVo). MTT, colony formation, and tumorigenicity assays were performed to analyze the effect of OPN downregulation on the in vitro and in vivo proliferation of CRC cells. Wound healing and Matrigel invasion assays were performed to analyze the effect of OPN downregulation on migration and invasion of CRC cells. A clonogenic cell survival assay after radiation was performed to analyze the effect of OPN downregulation on the radiosensitivity of CRC cells.
  
  
  RESULTS
  The relative level of OPN protein expression in CRC tissues was significantly higher than that in corresponding nontumor colon tissues (P < 0.05). We found that RNAi-mediated OPN downregulation could inhibit not only in vitro proliferation but also in vivo tumorigenicity of CRC cells. In addition, OPN downregulation could suppress in vitro invasion capacity and enhance in vitro radiosensitivity of CRC cells, which might be associated with decreased levels of MMP-2 and -9 expression.
  
  
  CONCLUSIONS
  RNAi-targeting OPN could inhibit proliferation, invasion and enhance radiosensitivity of human CRC cells. Therefore, OPN could serve as a novel molecular target for gene therapy of CRC.
authors.affiliation: Department of Infection, Beijing Friendship Hospital, Capital Medical University, 95 Yong-An Road, Beijing 100050, People's Republic of China. kui_li2008@yahoo.com.cn
authors.forename: Wang
authors.initials: W
authors.lastname: Likui
authors.forename: Wang
authors.initials: W
authors.lastname: Hong
authors.forename: Zhang
authors.initials: Z
authors.lastname: Shuwen
authors.forename: You
authors.initials: Y
authors.lastname: Yuangang
authors.forename: Wen
authors.initials: W
authors.lastname: Yan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000503:physiopathology / Q000532:radiotherapy; D015536:Down-Regulation; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053495:Osteopontin / Q000378:metabolism* / Q000502:physiology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011836:Radiation Tolerance; D014410:Tumor Stem Cell Assay
chemical_list: D012333:RNA, Messenger; D053495:Osteopontin