Irsan Istan, Akisue Toshihiro, Hara Hitomi, Fujimoto Takuya, Imabori Masaya, Doita Minoru, Kuroda Ryosuke, Fujioka Hiroyuki, Kawamoto Teruya, Yamamoto Tetsuji, Kurosaka Masahiro
Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, Hyogo, Japan.
Anticancer Res. 2007 Jan-Feb;27(1A):423-9.
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.
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.
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.
Imatinib mesylate reduced in vivo tumor growth of MFH that express PDGFRs and c-Kit associated with phosphorylation suppression.
恶性纤维组织细胞瘤（MFH）是成人软组织肉瘤中最具侵袭性且弥漫性生长的肿瘤之一，但从分子角度来看其特征仍不明确。甲磺酸伊马替尼是一种酪氨酸激酶抑制剂，可选择性抑制MFH细胞增殖。此前已检测了血小板衍生生长因子受体（PDGFRs）和c-Kit在MFH细胞系中的表达，并测试了甲磺酸伊马替尼对MFH细胞增殖的抑制作用。MFH细胞系显示出PDGFRs和c-Kit表达的多种模式。甲磺酸伊马替尼抑制表达PDGFRs和/或c-Kit的MFH细胞的增殖。
使用了四种MFH细胞系（奈良H、奈良F、GBS-1和TNMY1）。采用逆转录聚合酶链反应（RT-PCR）分析PDGFRs和c-Kit的mRNA表达；采用MTS法分析细胞增殖。免疫组织化学用于分析甲磺酸伊马替尼在体内对PDGFRs和c-Kit磷酸化的抑制作用。将奈良H和TNMY1细胞系接种到裸鼠体内，通过测量肿瘤结节的二维直径每日评估肿瘤生长情况。
PDGFRs和c-Kit在奈良F、GBS-1和TNMY1细胞中表达，但在奈良H细胞中不表达。甲磺酸伊马替尼抑制TNMY1细胞中PDGFRs和c-Kit的磷酸化，影响其致瘤性，对照组（标准差139立方毫米±1.03）和治疗组（标准差126.2立方毫米±1.63），但不影响奈良H细胞的致瘤性。
甲磺酸伊马替尼可降低表达PDGFRs和c-Kit的MFH的体内肿瘤生长，并与磷酸化抑制相关。
