title: Imatinib mesylate inhibits tumorigenicity of malignant fibrous histiocytoma cells in vivo.
abstract: BACKGROUND
  Malignant fibrous histiocytoma (MFH) is one of the most diffuse and aggressive tumors among soft tissue sarcomas in adults, but still poorly characterized from the molecular viewpoint. MFH cell proliferation is inhibited selectively by imatinib mesylate, a tyrosine kinase inhibitor. The expressions of platelet-derived growth factor receptors (PDGFRs) and c-Kit have been previously examined in MFH cell lines and the inhibitory effect of imatinib mesylate on the MFH cell proliferation was tested. MFH cell lines showed various patterns of PDGFRs and c-Kit expression. Imatinib mesylate inhibited the proliferation of MFH cells that expressed PDGFRs and/or c-Kit.
  
  
  METHODS
  Four MFH cell lines were used (Nara H, Nara F, GBS-1 and TNMY1). The mRNA expression of PDGFRs and c-Kit was analyzed using RT-PCR; cell proliferation was analyzed using the MTS assay. Immunohistochemistry was used to analyze the inhibitory effect of imatinib mesylate on phosphorylation of PDGFRs and c-Kit in vivo. The Nara H and TNMY1 cell lines were implanted into nude mice and tumor growth was evaluated daily by measuring the two-dimensional diameters of the tumor nodule.
  
  
  RESULTS
  PDGFRs and c-Kit were expressed in Nara F, GBS-1 and TNMY1, but not in Nara H cells. Imatinib mesylate inhibited PDGFRs and c-Kit phosphorylation in TNMY1 cells affecting the tumorigenicity, in the control group (139 mm3 SD +/- 1.03) and treatment group (126.2 mm3 SD +/- 1.63) but did not affect the tumorigenicity of Nara H cells.
  
  
  CONCLUSIONS
  Imatinib mesylate reduced in vivo tumor growth of MFH that express PDGFRs and c-Kit associated with phosphorylation suppression.
authors.affiliation: Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Istan
authors.initials: I
authors.lastname: Irsan
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akisue
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hara
authors.forename: Takuya
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Masaya
authors.initials: M
authors.lastname: Imabori
authors.forename: Minoru
authors.initials: M
authors.lastname: Doita
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujioka
authors.forename: Teruya
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D051677:Histiocytoma, Malignant Fibrous / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta