Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma

Abstract

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.

Nerve Growth Factor and Vascular Endothelial Growth Factor: Retrospective Analysis of 63 Patients with Salivary Adenoid Cystic Carcinoma

“…There is increasing evidence showing that overexpression of NGF results in enhanced invasiveness of a variety of cancer cells and a worse prognosis (Fuminori et al, 2001;Zhu et al, 2002;Tsunoda et al 2006). Moreover, previous studies found that NGF and its receptor were expressed in ACC tissue, and the expression levels were not the same between the solid and the cribriform-tubular type which was considered less aggressive, compared with the former (Sung et al, 2003;Zhu et al, 2003).…”

“…Recently, a few experiments have shown that NGF or its receptor is highly expressed in some malignancies with neurotropism such as prostatic carcinoma, and NGF is also specifically elevated in oral squamous cell carcinoma with perineural invasion (Fanburg-Smith and Miettinen, 2001;Fuminori, et al, 2001;Kolokythas et al 2006), indicating that this factor is relevant to neurotropism. In addition, NGF overexpression is associated with lymph node metastasis, distant metastasis, higher TNM stage and lowered survival of patients with squamous cell carcinoma of head and neck (Tsunoda et al, 2006).…”

Methylation of CLDN6, FBN2, RBP1, RBP4, TFPI2, and TMEFF2 in esophageal squamous cell carcinoma

“…Triplicate cultures of the esophageal squamous cell carcinoma cell line OE21 were grown in RPMI-1640, supplemented with 10% fetal bovine serum (FBS), at 37˚C in air with 5% CO 2 . Triplicate cultures of the esophageal squamous cell carcinoma cell lines KYSE-170, KYSE-510, KYSE-1170 (11,12) were grown in Ham's F-12/RPMI-1640 with 2% FBS at 37˚C in air with 5% CO 2 , and SUm/c (12) the same except for 5% FBS.…”

ABCG2 Expression Is an Independent Unfavorable Prognostic Factor in Esophageal Squamous Cell Carcinoma

“…The amount of RNA extracted from each sample was spectrophotometrically measured using a Gene Quanto Pro (Amersham Biosciences, Piscataway, N.J., USA). Then, precisely 5 µg from each of the extracted RNA samples was used for first-strand cDNA synthesis using a first-strand cDNA synthesis kit (GE Healthcare Bio-Sciences Corp., Piscataway, N.J., USA) according to the manufacturer’s instructions as described previously [15]. Specifically, Tris-EDTA solution was added to 5 µg of extracted RNA to adjust each of the reaction mixtures to the final volume of 8 µl and the mixture was denatured in 65°C for 10 min and incubated on ice for 2 min.…”