Inhibition of connective tissue growth factor (CTGF/CCN2) expression decreases the survival and myogenic differentiation of human rhabdomyosarcoma cells
Inhibition of connective tissue growth factor (CTGF/CCN2) expression decreases the survival and myogenic differentiation of human rhabdomyosarcoma cells
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DOI：
10.1158/0008-5472.can-3502-02
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发表时间：
2004-03-01
期刊：
影响因子：
11.2
通讯作者：
Lollini, PL
中科院分区：
文献类型：
--
作者：
Croci, S;Landuzzi, L;Lollini, PL
结缔组织生长因子（CTGF/CCN 2），CCN（Cyr 61，CTGF，Nov）基因家族的富含半胱氨酸的蛋白质，出现在由人横纹肌肉瘤细胞表达的基因的微阵列筛选。横纹肌肉瘤是一种起源于骨骼肌细胞的儿童软组织肉瘤。本研究旨在探讨CTGF在横纹肌肉瘤中的作用。胚胎型（RD/12、RD/18、CCA）和腺泡型（RMZ-RC 2、SJ-RH 4、SJ-RH 30）的人横纹肌肉瘤细胞、横纹肌肉瘤肿瘤标本和正常骨骼肌细胞表达CTGF。为了确定CTGF的功能，我们用CTGF反义寡核苷酸或CTGF小干扰RNA（siRNA）处理横纹肌肉瘤细胞。这两种治疗方法都抑制了横纹肌肉瘤细胞的生长，表明存在一个基于CTGF的新的自分泌环。CTGF反义寡核苷酸介导的生长抑制是由于细胞凋亡的显着增加，而细胞增殖是不变的。CTGF反义寡核苷酸诱导横纹肌肉瘤细胞肌样分化水平的强烈下降，而加入重组CTGF显着增加肌球蛋白阳性细胞的比例。CTGF作为一种生存和分化因子，可能成为横纹肌肉瘤治疗的新靶点。
Connective tissue growth factor (CTGF/CCN2), a cysteine-rich protein of the CCN (Cyr61, CTGF, Nov) family of genes, emerged from a microarray screen of genes expressed by human rhabdomyosarcoma cells. Rhabdomyosarcoma is a soft tissue sarcoma of childhood deriving from skeletal muscle cells. In this study, we investigated the role of CTGF in rhabdomyosarcoma. Human rhabdomyosarcoma cells of the embryonal (RD/12, RD/18, CCA) and the alveolar histotype (RMZ-RC2, SJ-RH4, SJ-RH30), rhabdomyosarcoma tumor specimens, and normal skeletal muscle cells expressed CTGF. To determine the function of CTGF, we treated rhabdomyosarcoma cells with a CTGF antisense oligonucleotide or with a CTGF small interfering RNA (siRNA). Both treatments inhibited rhabdomyosarcoma cell growth, suggesting the existence of a new autocrine loop based on CTGF. CTGF antisense oligonucleotide-mediated growth inhibition was specifically due to a significant increase in apoptosis, whereas cell proliferation was unchanged. CTGF antisense oligonucleotide induced a strong decrease in the level of myogenic differentiation of rhabdomyosarcoma cells, whereas the addition of recombinant CTGF significantly increased the proportion of myosin-positive cells. CTGF emerges as a survival and differentiation factor and could be a new therapeutic target in human rhabdomyosarcoma.