title: Effects of an Engineered Anti-HER2 Antibody chA21 on Invasion of Human Ovarian Carcinoma Cell In Vitro.
abstract: OBJECTIVE
  HER-2 plays an important role in the development and progression of ovarian carcinoma. A number of monoclonal antibodies (MAbs) and engineered antibody fragments (such as scFvs) against the subdomain II or IV of HER-2 extracellular domain (ECD) have been developed. We investigated the effect of chA21, an engineered anti-HER-2 antibody that bind primarily to subdomain I, on ovarian carcinoma cell invasion in vitro, and explored its possible mechanisms.
  
  
  METHODS
  Growth inhibition of SK-OV-3 cells was assessed using a Methyl thiazolyl tetrazolium (MTT) assay. The invasion ability of SK-OV-3 was determined by a Transwell invasion assay. The expression of matrix metalloproteinase-2 (MMP-2) and its tissue inhibitors (TIMP-2) was detected by immunocytochemical staining, and the expression of p38 and the phosphorylation of p38 were assayed by both immunocytochemistry and Western blot.
  
  
  RESULTS
  After treatment with chA21, the invasion of human ovarian cancer SK-OV-3 cells was inhibited in dose- and time-dependent manners. Simultaneously the expression of p38, phospho-p38, MMP-2 and the MMP-2/TIMP-2 ratio decreased, while TIMP-2 expression increased. Additionally, the decrease in phospho-p38 was much greater than that of p38.
  
  
  CONCLUSIONS
  chA21 may inhibit SK-OV-3 cell invasion via the signal transduction pathway involving MMP-2, TIMP-2, p38 and the activation of p38MAPK.
authors.affiliation: Department of Pathology, Anhui Medical University, Hefei 230032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Zheng-Sheng
authors.initials: ZS
authors.lastname: Wu
authors.forename: Gui-Hong
authors.initials: GH
authors.lastname: Zhang
authors.forename: An-Li
authors.initials: AL
authors.lastname: Zhang
keywords: HER-2; Invasion; Matrix metalloproteinase-2; Ovarian neoplasms; Tissue inhibitor of matrix metalloproteinase-2; p38 mitogen-activated protein kinase