Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma.
Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma.
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DOI：
10.1038/sj.bjc.6603255
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发表时间：
2006-08-07
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
神经生长因子（Nerve growth factor，NGF）不仅在神经系统中过度表达，而且在多种肿瘤中也存在过度表达。然而，神经生长因子在食管鳞状细胞癌（OESCC）中的作用仍不清楚。在此，我们首次证明了NGF-TrkA自分泌环的存在以及NGF过度表达在食管鳞癌中的临床意义。对109例食管鳞癌组织的免疫组化研究显示，NGF过表达与淋巴结转移、远处转移、TNM分期、肿瘤分化程度和生存率有关，其中63例（57.8%）为过度表达。NGF过表达还与TrkA的强表达和低亲和力神经营养因子受体（p75 NTR）的阴性表达相关。半定量逆转录-聚合酶链反应（RT-PCR）的19例手术标本显示17（89%）例患者的NGF mRNA上调。所有5个OESCC细胞系在体外检测分泌可检测的NGF在酶联免疫吸附试验，并表达TrkA和p75 NTR在RT-PCR和Western blot。在transwell迁移实验中，中和抗NGF抗体、TrkA抑制剂或NGF-小干扰RNA均能显著降低过表达NGF的食管鳞癌细胞系HSA/c的运动能力。我们的研究结果表明，神经生长因子是潜在的利益，不仅作为一个预后因素，但也作为一个新的治疗靶点在食管鳞癌。
Nerve growth factor (NGF) is overexpressed not only in nervous system, but also in several types of cancers. However, the role of NGF in oesophageal squamous cell carcinoma (OESCC) remains unclear. Here, we show the first evidence of NGF-TrkA autocrine loop and clinical significance of NGF overexpression in OESCC. Immunohistochemical study of 109 OESCC specimens revealed that NGF overexpression, found in 63 out of 109 patients (57.8%), was associated with lymph node metastasis, distant metastasis, higher TNM stage, poorer tumour differentiation, and poorer survival. NGF overexpression was also associated with strong expression of TrkA and negative expression of low-affinity neurotrophin receptor (p75NTR). Semiquantitative reverse transcription–polymerase chain reaction (RT–PCR) of 19 surgical specimens showed upregulation of NGF mRNA in 17 out of 19 (89%) patients. All five OESCC cell lines tested in vitro secreted detectable NGF in enzyme-linked immunosorbent assay, and expressed TrkA and p75NTR on RT–PCR and Western blot. The motility of HSA/c, one of the OESCC cell lines overexpressing NGF, was significantly decreased by either neutralising anti-NGF antibody, an inhibitor of TrkA, or NGF-small interfering RNA in transwell migration assay. Our findings suggest that NGF is of potential interest not only as a prognostic factor, but also as a novel therapeutic target in OESCC.
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影响因子：
8
作者：
Dollé, L;El Yazidi-Belkoura, I;Hondermarck, H
通讯作者：
Hondermarck, H
影响因子：
9.2
作者：
Estrach, S;Schmidt, S;Debant, A
通讯作者：
Debant, A
DOI：
10.1073/pnas.93.11.5466
发表时间：
1996-05-28
影响因子：
11.1
作者：
Debant, A;SerraPages, C;Streuli, M
通讯作者：
Streuli, M
影响因子：
56.9
作者：
LEVIMONTALCINI, R
通讯作者：
LEVIMONTALCINI, R
影响因子：
4.8
作者：
PFLUG, BR;DIONNE, C;DJAKIEW, D
通讯作者：
DJAKIEW, D