Zhu Zhaowen, Kleeff Jörg, Kayed Hany, Wang Li, Korc Murray, Büchler Markus W, Friess Helmut
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Mol Carcinog. 2002 Nov;35(3):138-47. doi: 10.1002/mc.10083.
Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain non-neuronal tumors. In pancreatic cancer NGF is overexpressed, and this overexpression is associated with increased perineural invasion. NGF has the potential to stimulate the growth of some pancreatic cancer cell lines, and this effect is mediated by the phosphorylation of tyrosine kinase receptor A and mitogen-activated protein kinase activation; it is dependent on the expression levels of tyrosine kinase receptor A and p75 receptors. To determine whether cancer cell-derived NGF can participate in the regulation of pancreatic cancer cell proliferation, PANC-1 human pancreatic cancer cells were stably transfected with a full-length human beta-NGF expression vector. In vitro and in vivo growth characteristics were analyzed by proliferation assays and invasion assays and in a nude mouse tumor model. Stable transfection of NGF in PANC-1 cells resulted in enhanced anchorage-dependent growth, with a decrease in doubling times of up to 50%, and in an approximately twofold increase in anchorage-independent cell growth and cell invasion. Furthermore, stably transfected PANC-1 cells showed enhanced tumorigenicity in nude mice. These results suggest that NGF has the capacity to act in a paracrine and/or an autocrine manner in pancreatic cancer and that it enhances cancer cell growth and invasion in vivo, thereby contributing to the aggressiveness and poor prognosis of this disease.
神经生长因子（NGF）对神经元肿瘤和某些非神经元肿瘤具有刺激和抑制作用。在胰腺癌中，NGF过度表达，且这种过度表达与神经周围浸润增加有关。NGF有可能刺激某些胰腺癌细胞系的生长，这种作用是由酪氨酸激酶受体A的磷酸化和丝裂原活化蛋白激酶的激活介导的；它取决于酪氨酸激酶受体A和p75受体的表达水平。为了确定癌细胞衍生的NGF是否能参与胰腺癌细胞增殖的调节，用全长人β-NGF表达载体稳定转染PANC-1人胰腺癌细胞。通过增殖试验、侵袭试验以及裸鼠肿瘤模型分析体外和体内生长特性。在PANC-1细胞中稳定转染NGF导致贴壁依赖性生长增强，倍增时间减少高达50%，非贴壁依赖性细胞生长和细胞侵袭增加约两倍。此外，稳定转染的PANC-1细胞在裸鼠中显示出更强的致瘤性。这些结果表明，NGF在胰腺癌中具有以旁分泌和/或自分泌方式发挥作用的能力，并且它在体内增强癌细胞的生长和侵袭，从而导致这种疾病的侵袭性和不良预后。
