Basic fibroblast growth factor in the bone microenvironment enhances cell motility and invasion of Ewing's sarcoma family of tumours by activating the FGFR1-PI3K-Rac1 pathway.
Basic fibroblast growth factor in the bone microenvironment enhances cell motility and invasion of Ewing's sarcoma family of tumours by activating the FGFR1-PI3K-Rac1 pathway.
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DOI：
10.1038/sj.bjc.6605775
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发表时间：
2010-07-27
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
尤文氏肉瘤家族肿瘤（ESFT）是一种骨和软组织的恶性小圆细胞肿瘤。其特征在于具有强烈的侵袭和形成转移的倾向。骨髓的微环境是许多生长因子的大型储存库，包括碱性成纤维细胞生长因子（bFGF）。然而，bFGF在ESFT侵袭和转移表型中的作用尚未研究。通过伤口愈合试验、趋化试验和侵袭试验评估ESFT细胞的运动性和侵袭性。采用RT-PCR、Western blotting和免疫组化方法检测ESFT细胞系和临床标本中FGF受体（FGFRs）的表达和活化情况。用相差显微镜和肌动蛋白荧光染色观察ESFT细胞的形态。通过下拉测定分析Rac 1的活化。bFGF可明显促进ESFT细胞的运动和侵袭。此外，发现FGFR 1在ESFT的临床样品中表达并活化。碱性FGF诱导的细胞运动通过FGFR 1-磷脂酰肌醇3-激酶（PI 3 K）-Rac 1途径介导。来自骨髓基质细胞的条件培养基通过激活bFGF/FGFR 1信号传导诱导ESFT细胞的运动。骨微环境中的bFGF-FGFR 1-PI 3 K-Rac 1通路可能在ESFT的侵袭和转移中起重要作用。
Ewing's sarcoma family of tumours (ESFT) is a malignant small round-cell tumour of the bone and soft tissues. It is characterised by a strong tendency to invade and form metastases. The microenvironment of the bone marrow is a large repository for many growth factors, including the basic fibroblast growth factor (bFGF). However, the role of bFGF in the invasive and metastatic phenotype of ESFT has not been investigated. The motility and invasion of ESFT cells were assessed by a wound-healing assay, chemotaxis assay, and invasion assay. The expression and activation of FGF receptors (FGFRs) in ESFT cell lines and clinical samples were detected by RT–PCR, western blotting, and immunohistochemistry. The morphology of ESFT cells was investigated by phase-contrast microscopy and fluorescence staining for actin. Activation of Rac1 was analysed by a pull-down assay. bFGF strongly induced the motility and invasion of ESFT cells. Furthermore, FGFR1 was found to be expressed and activated in clinical samples of ESFT. Basic FGF-induced cell motility was mediated through the FGFR1–phosphatidylinositol 3-kinase (PI3K)–Rac1 pathway. Conditioned medium from bone marrow stromal cells induced the motility of ESFT cells by activating bFGF/FGFR1 signalling. The bFGF–FGFR1–PI3K–Rac1 pathway in the bone microenvironment may have a significant role in the invasion and metastasis of ESFT.
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影响因子：
3.8
作者：
Tchou-Wong KM;Fok SY;Rubin JS;Pixley F;Condeelis J;Braet F;Rom W;Soon LL
通讯作者：
Soon LL
影响因子：
6.2
作者：
Bozzi, Fabio;Tamborini, Elena;Pilotti, Silvana
通讯作者：
Pilotti, Silvana
影响因子：
3
作者：
Korc M;Friesel RE
通讯作者：
Friesel RE
DOI：
10.1016/j.biocel.2008.11.008
发表时间：
2009-06-01
影响因子：
4
作者：
Chalkiadaki, Georgia;Nikitovic, Dragana;Tzanakakis, George N.
通讯作者：
Tzanakakis, George N.
影响因子：
4
作者：
Hanada, M;Tanaka, K;Iwamoto, Y
通讯作者：
Iwamoto, Y