GDNF与消化系统肿瘤关系研究进展

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (7): 986-989.

GDNF与消化系统肿瘤关系研究进展

王小娟, 李小丽, 金正旭, 张德奎^*

兰州大学第二医院消化内科, 甘肃兰州 730000

收稿日期:2019-10-24 修回日期:2020-03-22 出版日期:2020-07-05 发布日期:2020-06-29
通讯作者: ^*sczdk1972@163.com
基金资助:
国家自然科学基金(81470808)

Research of relation between glial cell line-derived neurotrophic factor and digestive system tumor

WANG Xiao-juan, LI Xiao-li, JIN Zheng-xu, ZHANG De-kui^*

Department of Gastroenterology, the Second Hospital of Lanzhou University, Lanzhou 730000, China

Received:2019-10-24 Revised:2020-03-22 Online:2020-07-05 Published:2020-06-29
Contact: ^*sczdk1972@163.com

摘要/Abstract

摘要： 肠神经胶质细胞源性神经生长因子(GDNF)及其受体(RET)的异常表达与消化系统肿瘤的发生、发展及预后相关。胰腺癌中,GDNF及其受体RET与周围神经侵袭相关并呈剂量依赖性,RET(-)癌细胞则失去了侵袭并且破坏神经的能力;结肠癌中,RET突变促进结肠癌细胞增殖、迁移及存活,且与结肠癌患者预后较差相关;肝癌中,GDNF可独立于血管源性生长因子促进肝癌组织血管生成,为肿瘤细胞的增殖侵袭提供充足的营养;胃癌中发现GFRα3启动子区域甲基化,且其程度和术后患者存活率之间呈反比关系。

关键词: 肠神经胶质细胞源性神经营养因子, 肝癌, 结直肠癌, 胰腺癌, 胃癌

Abstract: Abnormal expression of GDNF (glial cell line-derived neurotrophic factor) and its receptor(RET) are associated with the emergence and development of tumors in the digestive system. GDNF and RET are associated with peripheral nerve invasion with a dose-dependent manner in pancreatic cancer, while RET(-) cancer cells lose the ability to invade and destroy nerves. RET mutations promote the proliferation, migration and survival of colon cancer cells, and are associated with poor prognosis of colon cancer patients. GDNF can promote the angiogenesis of liver cancer tissues independently of vasogenic growth factor, providing sufficient nutrition for the growth and invasion of tumor cells. Methylation of the GFR 3 promoter was found in gastric cancer, and the degree of methylation was negatively related to postoperative survival of patients.

Key words: glial cell line-derived neurotrophic factor(GDNF), liver cancer, colorectal cancer, pancreatic cancer, gastric cancer

中图分类号:

R735

王小娟, 李小丽, 金正旭, 张德奎. GDNF与消化系统肿瘤关系研究进展[J]. 基础医学与临床, 2020, 40(7): 986-989.

WANG Xiao-juan, LI Xiao-li, JIN Zheng-xu, ZHANG De-kui. Research of relation between glial cell line-derived neurotrophic factor and digestive system tumor[J]. Basic & Clinical Medicine, 2020, 40(7): 986-989.

参考文献

[1] Lin LF, Doherty DH, Lile JD, et al. GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons[J]. Science, 1993, 260:1130-1132.
[2] Simons M, Gordon E, Claesson-Welsh L. Mechanisms and regulation of endothelial VEGF receptor signalling[J]. Nat Rew Mol Cell Biol, 2016, 17:611-625.
[3] Zhong Z, Gu H, Peng J, et al. GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis[J]. Oncotarget, 2016, 7:36829-36841.
[4] Penttinen AM, Parkkinen I, Voutilainen MH, et al. Pre-α-pro-GDNF and Pre-β-pro-GDNF isoforms are neuroprotective in the 6-hydroxydopamine rat model of Parkinson's disease[J]. Front Neurol, 2018, 9:457.
[5] Ochoa-Cortes F, Turco F, Linan-Rico A,et al. Enteric glial cells: A new frontier in neurogastroenterology and clinical target for inflammatory bowel diseases[J]. Inflamm Bowel Dis, 2016, 22:433-449.
[6] Luo P, Liu D, Li C, et al. Enteric glial cell activation protects enteric neurons from damage due to diabetes in part via the promotion of neurotrophic factor release[J]. Neurogastroenterol Motil, 2018, 30:e13368.doi:10.1111/nmo.13368.
[7] Bauman BD, Meng J, Zhang L, et al. Enteric glial-mediated enhancement of intestinal barrier integrity is compromised by morphine[J]. J Surg Res, 2017, 219:214-221.
[8] Gardaneh M, Shojaei S, Kaviani A, et al. GDNF induces RET-SRC-HER2-dependent growth in trastuzumab-sensitive but SRC-independent growth in resistant breast tumor cells[J]. Breast Cancer Res Treat,2017, 162:231-241.
[9] Shabtay-Orbach A, Amit M, Binenbaum Y, et al. Paracrine regulation of glioma cells invasion by astrocytes is mediated by glial-derived neurotrophic factor[J]. Int J Cancer, 2015, 137:1012-1020.
[10] Bespalov MM, Sidorova YA, Tumova S, et al. Heparan sulfate proteoglycan syndecan-3 is a novel receptor for GDNF, neurturin, and artemin[J]. J Cell Biol, 2011, 192:153-169.
[11] Sidorova YA, Bespalov MM, Wong AW, et al. A novel small molecule GDNF receptor RET agonist, BT13, promotes neurite growth from sensory neurons in vitro and attenuates experimental neuropathy in the rat[J]. Front Pharmacol, 2017, 8:365.
[12] McKeown SJ, Mohsenipour M, Bergner AJ, et al. Stamp, exposure to GDNF enhances the ability of enteric neural progenitors to?Generate an enteric nervous system[J]. Stem Cell Reports, 2017, 8:476-488.
[13] Heuckeroth RO, Schäfer KH, Gene-environment interactions and the enteric nervous system: Neural plasticity and hirschsprung disease prevention[J]. Dev Biol, 2016, 417:188-197.
[14] Alrawashdeh W, Jones R, Dumartin L, et al. Perineural invasion in pancreatic cancer: proteomic analysis and in vitro modelling[J]. Mol Oncol, 2019, 13:1075-1091.
[15] Chen SH, Zhang BY, Zhou B, et al. Perineural invasion of cancer: A complex crosstalk between cells and mole-cules in the perineural niche[J]. Am J Cancer Res, 2019, 9:1-21.
[16] Lin C, Cao W, Ren Z, et al. GDNF secreted by nerves enhances PD-L1 expression via JAK2-STAT1 signaling activation in HNSCC[J]. Oncoimmunology, 2017, 6:e1353860.doi:10.1080/2162402X.2017.1353860.
[17] Baspinar S, Bircan S, Ciris M, et al. Expression of NGF, GDNF and MMP-9 in prostate carcinoma[J]. Pathol Res Pract, 2017, 213:483-489.
[18] Zhong F, Zhang W, Cao Y, et al. LncRNA NEAT1 promotes colorectal cancer cell proliferation and migration via regulating glial cell-derived neurotrophic factor by sponging miR-196a-5p[J]. Acta Biochim Biophys Sin (Shanghai), 2018, 50:1190-1199.
[19] Amit M, Na'ara S, Leider-Trejo L, et al. Upregulation of RET induces perineurial invasion of pancreatic adenocarcinoma[J].Oncogene, 2017, 36:3232-3239.
[20] Oliveira DM, Grillone K, Mignogna C, et al. Correction to: Next-generation sequencing analysis of receptor-type tyrosine kinase genes in surgically resected colon cancer: identification of gain-of-function mutations in the RET proto-oncogene[J]. J Exp Clin Cancer Res, 2018, 37:112.
[21] Gozgit JM, Chen TH, Song Y, et al. RET fusions observed in lung and colorectal cancers are sensitive to ponatinib[J].Oncotarget, 2018, 9:29654-29664.
[22] Kloosterman WP, Coebergh van den Braak RRJ, Pieterse M, et al. A systematic analysis of oncogenic gene fusions in primary colon cancer[J]. Cancer Res, 2017, 77:3814-3822.
[23] Eftang LL, Klajic J, Kristensen VN, et al. GFRA3 promoter methylation may be associated with decreased postoperative survival in gastric cancer[J]. BMC Cancer, 2016, 16:225.doi:10.1186/s12885-016-2247-8.
[24] FDA授予Loxo Oncology公司在研药物LOXO-292突破性疗法认定[J]. 临床合理用药杂志, 2018, 11:98.
[25] Simons M, Gordon E, Claesson-Welsh L. Mechanisms and regulation of endothelial VEGF receptor signalling[J]. Nat Rev Mol Cell Bio, 2016, 17:611-625.