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Clin Exp Metastas:MET和FN14促使肺癌转移扩散

来源:生物谷 2014-04-12 09:08

2014年4月11日讯 /生物谷BIOON/--根据Translational Genomics Research Institute (TGen)研究人员最近完成的一研究证实:两种细胞表面受体可能与最常见形式肺癌扩散到身体其他部位密切相关。

肝细胞生长因子受体(HGFR/MET)和成纤维细胞生长因子诱导14(FN14)与非小细胞肺癌(NSCLC)潜在的扩散有关,相关研究发表在4月8日的Clinical & Experimental Metastasis杂志上。

超过85%的肺癌为非小细胞肺癌,今年将杀死估计159,000名美国人,使得它成为癌症相关死亡的最首要原因,5年生存率不到10%。

非小细胞肺癌的侵袭和转移自然助长了这种高死亡率,因此发现侵袭和转移潜在的原因是帮助患者生存的关键。

针对MET和FN14,可以帮助停止或减缓这种肺癌的扩散,可能导致新的治疗方法。Timothy Whitsett博士表示:由于转移表型是肺癌死亡率的主要病因,理解并针对这些途径可以降低晚期肺癌高死亡率。

TGen研究发现,与原发性肺肿瘤相比,MET和FN14在转移性肿瘤升高,抑制MET激活或FN14表达能降低肿瘤细胞的侵袭。(生物谷Bioon.com)

 

doi:10.1007/s10585-014-9653-6
FN14 expression correlates with MET in NSCLC and promotes MET-driven cell invasion

Timothy G. Whitsett, Shannon P. Fortin Ensign, Harshil D. Dhruv, Landon J. Inge, Paul Kurywchak, Kerri K. Wolf, Janine LoBello, Christopher B. Kingsley, Jeffrey W. Allen, Glen J. Weiss,et al.

The five-year survival rate in advanced non-small cell lung cancer (NSCLC) remains below ten percent. The invasive and metastatic nature of NSCLC tumor cells contributes to the high mortality rate, and as such the mechanisms that govern NSCLC metastasis is an active area of investigation. Two surface receptors that influence NSCLC invasion and metastasis are the hepatocyte growth factor receptor (HGFR/MET) and fibroblast growth factor-inducible 14 (FN14). MET protein is over-expressed in NSCLC tumors and associated with poor clinical outcome and metastasis. FN14 protein is also elevated in NSCLC tumors and positively correlates with tumor cell migration and invasion. In this report, we show that MET and FN14 protein expressions are significantly correlated in human primary NSCLC tumors, and the protein levels of MET and FN14 are elevated in metastatic lesions relative to patient-matched primary tumors. In vitro, HGF/MET activation significantly enhances FN14 mRNA and protein expression. Importantly, depletion of FN14 is sufficient to inhibit MET-driven NSCLC tumor cell migration and invasion in vitro. This work suggests that MET and FN14 protein expressions are associated with the invasive and metastatic potential of NSCLC. Receptor-targeted therapeutics for both MET and FN14 are in clinical development, the use of which may mitigate the metastatic potential of NSCLC.

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