Rasi Guido, Serafino Annalucia, Bellis Lia, Lonardo Maria Teresa, Andreola Federica, Zonfrillo Manuela, Vennarecci Giovanni, Pierimarchi Pasquale, Sinibaldi Vallebona Paola, Ettorre Giuseppe Maria, Santoro Eugenio, Puoti Claudio
National Research Council, Istituto di Neurobiologia e Medicina Molecolare, Via Fosso del Cavaliere 100, 00133 Rome, Italy.
World J Gastroenterol. 2007 Oct 7;13(37):4986-95. doi: 10.3748/wjg.v13.i37.4986.
To define NGF (nerve growth factor) and its high-affinity receptor trkA(NGF) presence and distribution in fibrotic liver and in HCC, and to verify if NGF might have a role in fibrosis and HCC.
Intracellular distribution of NGF and trkA(NGF) were assessed by immunohistochemistry and immuno-electron microscopy in liver specimens from HCC, cirrhosis or both. ELISA was used to measure circulating NGF levels.
NGF and trkA(NGF) were highly expressed in HCC tissue, mainly localized in hepatocytes, endothelial and some Kupffer cells. In the cirrhotic part of the liver they were also markedly expressed in bile ducts epithelial and spindle-shaped cells. Surprisingly, in cirrhotic tissue from patients without HCC, both NGF and trkA(NGF) were negative. NGF serum levels in cirrhotic and/or HCC patient were up to 25-fold higher than in controls.
NGF was only detected in liver tissue with HCC present. Intracellular distribution suggests paracrine and autocrine mechanisms of action. Better definition of mechanisms may allow for therapeutic and diagnostic/prognostic use of NGF.
确定神经生长因子（NGF）及其高亲和力受体酪氨酸激酶A（trkA）（NGF）在肝纤维化和肝癌组织中的存在及分布情况，并验证NGF是否在肝纤维化和肝癌中发挥作用。
采用免疫组织化学和免疫电子显微镜技术评估肝癌、肝硬化或同时患有这两种疾病的患者肝脏标本中NGF和trkA（NGF）的细胞内分布情况。采用酶联免疫吸附测定（ELISA）法检测循环血中NGF水平。
NGF和trkA（NGF）在肝癌组织中高表达，主要定位于肝细胞、内皮细胞和部分库普弗细胞。在肝脏的肝硬化部分，它们在胆管上皮细胞和梭形细胞中也有明显表达。令人惊讶的是，在无肝癌患者的肝硬化组织中，NGF和trkA（NGF）均为阴性。肝硬化和/或肝癌患者的血清NGF水平比对照组高25倍。
仅在存在肝癌的肝组织中检测到NGF。细胞内分布提示其旁分泌和自分泌作用机制。对作用机制更清晰的界定可能有助于NGF在治疗及诊断/预后方面的应用。
