The Severity of Neural Invasion Is Associated with Shortened Survival in Colon Cancer
The Severity of Neural Invasion Is Associated with Shortened Survival in Colon Cancer
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DOI：
10.1158/1078-0432.ccr-12-2392
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发表时间：
2013-01-01
影响因子：
11.5
通讯作者：
Ceyhan, Guealp O.
中科院分区：
文献类型：
--
作者：
Liebl, Florian;Demir, Ihsan Ekin;Ceyhan, Guealp O.
目的：神经浸润（NI）是结肠癌的一个组织病理学特征，但很少被考虑。因此，我们进行了结肠癌NI的形态和功能的表征。实验设计：NI在673例结肠癌患者进行了调查。确定NI的部位和严重程度，并与患者的预后和生存有关。在体外三维（3D）-神经-迁移测定中将结肠癌细胞（HT 29、HCT-116、SW 620和DLD-1）的神经-亲和力与胰腺癌（T3 M4和SU 86.86）和直肠癌细胞（CMT-93）进行比较，并通过活细胞成像进行分析。在结肠癌和胰腺癌神经中定量神经可塑性标志物GAP-43和神经营养化学引诱因子Artemin和神经生长因子（NGF）的免疫反应性。结果：673例中有210例（31.2%）出现NI。尽管NI严重程度评分的增加与生存率显著降低相关，但NI的存在并不是结肠癌的独立预后因素。在3D迁移试验中，结肠癌和直肠癌细胞与胰腺癌细胞相比显示出更少的神经突靶向迁移。胰腺癌和直肠癌细胞的上清液诱导的神经突密度比结肠癌细胞的高得多。因此，神经生长因子，Artemin，GAP-43在胰腺癌的神经比在结肠cancer.Conclusion：NI是不是一个独立的预后因素在结肠癌。结肠癌细胞和神经元之间缺乏相当大的生物亲和力，结肠神经对化学引诱物分子的低表达谱，以及结肠癌中缺乏主要的神经可塑性，这些都可以解释结肠癌中NI的低患病率和影响。临床癌症研究; 19（1）; 50-61。(C)2012年AACR。
Purpose: Neural invasion (NI) is a histopathologic feature of colon cancer that receives little consideration. Therefore, we conducted a morphologic and functional characterization of NI in colon cancer.Experimental Design: NI was investigated in 673 patients with colon cancer. Localization and severity of NI was determined and related to patient's prognosis and survival. The neuro-affinity of colon cancer cells (HT29, HCT-116, SW620, and DLD-1) was compared with pancreatic cancer (T3M4 and SU86.86) and rectal cancer cells (CMT-93) in the in vitro three-dimensional (3D)-neural-migration assay and analyzed via live-cell imaging. Immunoreactivity of the neuroplasticity marker GAP-43, and the neurotrophic- chemoattractant factors Artemin and nerve growth factor (NGF), was quantified in colon cancer and pancreatic cancer nerves. Dorsal root ganglia of newborn rats were exposed to supernatants of colon cancer, rectal cancer, and pancreatic cancer cells and neurite density was determined.Results: NI was detected in 210 of 673 patients (31.2%). Although increasing NI severity scores were associated with a significantly poorer survival, presence of NI was not an independent prognostic factor in colon cancer. In the 3D migration assay, colon cancer and rectal cancer cells showed much less neuritetargeted migration when compared with pancreatic cancer cells. Supernatants of pancreatic cancer and rectal cancer cells induced a much higher neurite density than those of colon cancer cells. Accordingly, NGF, Artemin, and GAP-43 were much more pronounced in nerves in pancreatic cancer than in colon cancer.Conclusion: NI is not an independent prognostic factor in colon cancer. The lack of a considerable biologic affinity between colon cancer cells and neurons, the low expression profile of colonic nerves for chemoattractant molecules, and the absence of a major neuroplasticity in colon cancer may explain the low prevalence and impact of NI in colon cancer. Clin Cancer Res; 19(1); 50-61. (C) 2012 AACR.