摘要
背景:在过去的几年中,关于多肽参与癌症的科学兴趣有所增加。在肿瘤细胞中,多肽及其受体的过表达是已知的,并提出了治疗癌症的新的治疗靶点。神经紧张素能系统的过表达与不良预后、肿瘤大小、更高的肿瘤侵袭性、复发风险增加和对化疗药物的敏感性更差相关。目的:本综述的目的是更新有关神经紧张素能系统参与癌症的研究结果,以提出针对该系统的抗癌治疗策略。神经紧张素(NT)前体、NT及其受体(NTR),以及神经紧张素能系统在肺、乳腺癌、前列腺、胃、结肠、肝癌和胰腺癌、胶质母细胞瘤、神经内分泌肿瘤和b细胞白血病中的作用,以及NT介导的信号通路。未来将提出一些研究思路,如调节NT前体表达的分子,饮食在肿瘤发展中的影响,NT激活的分子和信号通路,以及针对神经紧张素能系统的抗肿瘤治疗策略。结论:NT通过NTR发挥致癌(肿瘤细胞增殖、侵袭、迁移、血管生成)和抗凋亡作用,而NTR拮抗剂则抑制这些作用。NTR表达可作为诊断工具/治疗靶点,而NTR拮抗剂作为抗肿瘤药物可作为治疗NTR过表达肿瘤的一种治疗策略。
关键词: 神经紧张素,神经紧张素受体拮抗剂,肿瘤,肺、乳腺、前列腺、胃肠、肝脏,信号通路。
[http://dx.doi.org/10.2991/jegh.k.191008.001] [PMID: 31854162]
[http://dx.doi.org/10.1007/s00726-014-1736-9] [PMID: 24705689]
[http://dx.doi.org/10.1038/s41598-017-04832-0] [PMID: 28676692]
[http://dx.doi.org/10.3390/ijms21103494] [PMID: 32429087]
[http://dx.doi.org/10.1038/bjp.2008.268] [PMID: 18587421]
[http://dx.doi.org/10.1002/ijc.26208] [PMID: 21630261]
[http://dx.doi.org/10.1016/j.peptides.2006.01.028] [PMID: 16904238]
[http://dx.doi.org/10.1016/j.canlet.2018.12.007] [PMID: 30583074]
[http://dx.doi.org/10.1016/j.peptides.2006.04.030] [PMID: 16887236]
[http://dx.doi.org/10.1002/psc.3093] [PMID: 29938867]
[http://dx.doi.org/10.4049/jimmunol.1501443] [PMID: 27076683]
[http://dx.doi.org/10.1016/j.ajpath.2014.08.015] [PMID: 25307345]
[http://dx.doi.org/10.1096/fj.202002547RR] [PMID: 33710668]
[http://dx.doi.org/10.1038/s41419-020-03245-8] [PMID: 33268796]
[http://dx.doi.org/10.1073/pnas.90.1.65] [PMID: 8380498]
[http://dx.doi.org/10.1053/j.gastro.2011.07.038] [PMID: 21806946]
[http://dx.doi.org/10.1038/s41388-019-0750-5] [PMID: 30770901]
[PMID: 9530155]
[http://dx.doi.org/10.1016/S0165-6147(99)01357-7] [PMID: 10390649]
[http://dx.doi.org/10.1210/endo-126-3-1584] [PMID: 2307120]
[http://dx.doi.org/10.1016/0143-4179(90)90047-3] [PMID: 2080018]
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb27335.x] [PMID: 1463268]
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb27337.x] [PMID: 1463273]
[http://dx.doi.org/10.1016/0300-9084(94)90147-3] [PMID: 7819324]
[http://dx.doi.org/10.1074/jbc.271.19.11368] [PMID: 8626691]
[http://dx.doi.org/10.1074/jbc.273.39.25339] [PMID: 9738000]
[http://dx.doi.org/10.1006/bbrc.1998.8506] [PMID: 9600085]
[http://dx.doi.org/10.1042/bj2910225] [PMID: 8471039]
[http://dx.doi.org/10.1016/0167-0115(93)90412-2] [PMID: 8426913]
[PMID: 1858034]
[http://dx.doi.org/10.1007/s00268-002-4055-3] [PMID: 11960215]
[http://dx.doi.org/10.1097/00000658-199308000-00010] [PMID: 8342998]
[PMID: 2859633]
[http://dx.doi.org/10.1111/ahe.12194] [PMID: 26250798]
[http://dx.doi.org/10.1016/S0021-9258(17)32938-1] [PMID: 993203]
[http://dx.doi.org/10.1136/gut.28.Suppl.19] [PMID: 3692307]
[PMID: 3202174]
[http://dx.doi.org/10.1016/0016-5085(92)91099-P] [PMID: 1612361]
[http://dx.doi.org/10.1016/j.biocel.2008.03.015] [PMID: 18456542]
[http://dx.doi.org/10.1016/j.bbadis.2017.12.036] [PMID: 29288794]
[http://dx.doi.org/10.1172/JCI70647] [PMID: 24531547]
[http://dx.doi.org/10.1523/JNEUROSCI.2269-05.2005] [PMID: 16221860]
[http://dx.doi.org/10.1016/j.pbb.2010.01.012] [PMID: 20122953]
[http://dx.doi.org/10.1016/S0140-6736(80)91434-8] [PMID: 6103384]
[http://dx.doi.org/10.1097/MED.0b013e3283419052] [PMID: 21124211]
[http://dx.doi.org/10.1016/j.peptides.2006.04.024] [PMID: 16891042]
[http://dx.doi.org/10.1152/ajpgi.00140.2004] [PMID: 15764810]
[PMID: 11734615]
[http://dx.doi.org/10.1523/JNEUROSCI.5376-03.2004] [PMID: 15014132]
[http://dx.doi.org/10.1016/S0306-4522(00)00448-6] [PMID: 11226674]
[http://dx.doi.org/10.1016/j.pain.2004.12.031] [PMID: 15733655]
[http://dx.doi.org/10.1037/0735-7044.103.4.765] [PMID: 2669837]
[http://dx.doi.org/10.1016/j.neubiorev.2017.09.003] [PMID: 28887225]
[http://dx.doi.org/10.1006/frne.1996.0146] [PMID: 9101258]
[http://dx.doi.org/10.1111/j.1748-1716.1984.tb07397.x] [PMID: 6741572]
[http://dx.doi.org/10.1371/journal.pone.0211134] [PMID: 30917119]
[http://dx.doi.org/10.1038/nature17662] [PMID: 27193687]
[PMID: 1887896]
[http://dx.doi.org/10.1016/j.peptides.2005.12.016] [PMID: 16872719]
[http://dx.doi.org/10.1080/13543776.2021.1866539] [PMID: 33393392]
[http://dx.doi.org/10.1124/mol.63.6.1256] [PMID: 12761335]
[http://dx.doi.org/10.1016/j.peptides.2006.04.027] [PMID: 16919370]
[http://dx.doi.org/10.1016/0006-8993(94)91737-X] [PMID: 8205478]
[http://dx.doi.org/10.1016/0896-6273(90)90137-5] [PMID: 1694443]
[http://dx.doi.org/10.1016/0014-5793(96)00397-3] [PMID: 8647296]
[http://dx.doi.org/10.1111/j.1476-5381.1994.tb13077.x] [PMID: 8075852]
[http://dx.doi.org/10.1523/JNEUROSCI.16-18-05613.1996] [PMID: 8795617]
[PMID: 9023294]
[http://dx.doi.org/10.1016/S0014-2999(98)00678-5] [PMID: 9851594]
[http://dx.doi.org/10.1073/pnas.0705312104] [PMID: 17620610]
[http://dx.doi.org/10.1016/j.bbrc.2009.12.007] [PMID: 19968961]
[http://dx.doi.org/10.1074/jbc.272.6.3599] [PMID: 9013611]
[http://dx.doi.org/10.1074/jbc.273.41.26273] [PMID: 9756851]
[http://dx.doi.org/10.3389/fphar.2018.01507] [PMID: 30666202]
[http://dx.doi.org/10.1038/nsmb.1543] [PMID: 19122660]
[http://dx.doi.org/10.1002/pro.2512] [PMID: 24985322]
[http://dx.doi.org/10.1038/nature02319] [PMID: 14985763]
[http://dx.doi.org/10.1523/JNEUROSCI.5123-04.2005] [PMID: 15930396]
[http://dx.doi.org/10.1523/JNEUROSCI.2059-09.2009] [PMID: 19940174]
[http://dx.doi.org/10.1038/s41419-019-1385-8] [PMID: 30741921]
[http://dx.doi.org/10.1016/j.biocel.2013.01.020] [PMID: 23395631]
[http://dx.doi.org/10.18632/genesandcancer.22] [PMID: 25221642]
[http://dx.doi.org/10.1038/s41467-017-01485-5] [PMID: 29167428]
[http://dx.doi.org/10.3390/cells2010124] [PMID: 24709648]
[http://dx.doi.org/10.1080/19420889.2015.1130192] [PMID: 27066187]
[http://dx.doi.org/10.1053/gast.2002.36000] [PMID: 12360476]
[http://dx.doi.org/10.1677/jme.1.01709] [PMID: 15956348]
[http://dx.doi.org/10.1016/S0304-3835(96)04466-7] [PMID: 9018081]
[http://dx.doi.org/10.1159/000229000] [PMID: 19752540]
[PMID: 16633328]
[http://dx.doi.org/10.1158/1078-0432.CCR-10-0659] [PMID: 20810387]
[http://dx.doi.org/10.18632/oncotarget.1633] [PMID: 25249545]
[http://dx.doi.org/10.1242/jcs.149336] [PMID: 25037567]
[http://dx.doi.org/10.1038/s41467-017-01172-5] [PMID: 29084952]
[http://dx.doi.org/10.1016/j.mehy.2017.09.003] [PMID: 29055389]
[http://dx.doi.org/10.1371/journal.pone.0004223] [PMID: 19156213]
[http://dx.doi.org/10.1111/j.1365-2559.1985.tb02968.x] [PMID: 2579885]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-0450] [PMID: 16778199]
[http://dx.doi.org/10.18632/oncotarget.3401] [PMID: 25871389]
[http://dx.doi.org/10.1074/jbc.M110.211714] [PMID: 22128158]
[http://dx.doi.org/10.1371/journal.pone.0097151] [PMID: 24824754]
[http://dx.doi.org/10.18632/oncotarget.1632] [PMID: 25249538]
[http://dx.doi.org/10.1073/pnas.91.11.4673] [PMID: 8197117]
[http://dx.doi.org/10.1016/S0196-9781(97)00306-9] [PMID: 9493857]
[http://dx.doi.org/10.1002/ijc.1225] [PMID: 11304684]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1646] [PMID: 21903767]
[http://dx.doi.org/10.3390/ijms20071721] [PMID: 30959962]
[http://dx.doi.org/10.1158/0008-5472.CAN-09-1252] [PMID: 20048080]
[http://dx.doi.org/10.1210/en.2014-1590] [PMID: 25365768]
[http://dx.doi.org/10.1016/j.matbio.2017.04.001] [PMID: 28433812]
[http://dx.doi.org/10.1186/s13000-015-0356-3] [PMID: 26215716]
[http://dx.doi.org/10.1152/ajpgi.2000.279.6.G1139] [PMID: 11093935]
[http://dx.doi.org/10.1006/bbrc.1994.2205] [PMID: 7521165]
[http://dx.doi.org/10.3892/ijo.2017.3990] [PMID: 28498396]
[http://dx.doi.org/10.1016/j.peptides.2008.04.014] [PMID: 18541341]
[http://dx.doi.org/10.1007/s13304-017-0464-6] [PMID: 28560510]
[http://dx.doi.org/10.1016/0960-7404(92)90025-G] [PMID: 1341243]
[http://dx.doi.org/10.1002/(SICI)1097-0215(19990129)80:3<448:AID-IJC19>3.0.CO;2-N] [PMID: 9935189]
[http://dx.doi.org/10.1371/journal.pone.0025097] [PMID: 21966426]
[http://dx.doi.org/10.18632/oncotarget.11854] [PMID: 27611941]
[http://dx.doi.org/10.1016/j.canlet.2016.11.032] [PMID: 27914862]
[http://dx.doi.org/10.1016/S0140-6736(84)90934-6] [PMID: 6199633]
[http://dx.doi.org/10.1002/hep.24739] [PMID: 21994122]
[http://dx.doi.org/10.1371/journal.pone.0056069] [PMID: 23418512]
[http://dx.doi.org/10.1007/BF01295980] [PMID: 7307861]
[http://dx.doi.org/10.1136/gut.42.4.546] [PMID: 9616318]
[http://dx.doi.org/10.1007/s00726-017-2430-5] [PMID: 28536844]
[http://dx.doi.org/10.1186/s13550-015-0094-2] [PMID: 25859423]
[http://dx.doi.org/10.1097/00000658-200006000-00008] [PMID: 10816627]
[http://dx.doi.org/10.1097/00000658-199305010-00003] [PMID: 8387763]
[http://dx.doi.org/10.1002/(SICI)1097-0142(19970501)79:9<1787:AID-CNCR22>3.0.CO;2-T] [PMID: 9128997]
[PMID: 17641415]
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00192] [PMID: 29889537]
[http://dx.doi.org/10.2967/jnumed.117.193847] [PMID: 29025990]
[http://dx.doi.org/10.1038/bjc.2017.126] [PMID: 28494471]
[http://dx.doi.org/10.1007/s10571-015-0172-z] [PMID: 25772140]
[http://dx.doi.org/10.1038/s41419-019-1449-9] [PMID: 30814514]
[http://dx.doi.org/10.18632/oncotarget.24102] [PMID: 29467963]
[http://dx.doi.org/10.1093/neuonc/not039] [PMID: 23576602]
[http://dx.doi.org/10.18632/oncotarget.4745] [PMID: 26298774]
[http://dx.doi.org/10.4049/jimmunol.1102937] [PMID: 23109725]
[http://dx.doi.org/10.1038/onc.2017.365] [PMID: 29059151]
[http://dx.doi.org/10.1124/mol.64.2.421] [PMID: 12869647]
[PMID: 19862492]
[http://dx.doi.org/10.1074/jbc.M110.192534] [PMID: 21212273]
[http://dx.doi.org/10.1074/jbc.M401453200] [PMID: 15247267]
[http://dx.doi.org/10.1006/bbrc.2000.2335] [PMID: 10720480]
[http://dx.doi.org/10.1124/mol.104.010801] [PMID: 15755906]
[http://dx.doi.org/10.1038/sj.onc.1209814] [PMID: 16862179]
[http://dx.doi.org/10.1002/pros.22624] [PMID: 23192379]
[http://dx.doi.org/10.1016/j.regpep.2004.03.004] [PMID: 15177934]
[http://dx.doi.org/10.1016/j.ejphar.2019.172735] [PMID: 31614143]
[http://dx.doi.org/10.18632/oncotarget.27149] [PMID: 31489118]
[http://dx.doi.org/10.1186/1471-2407-11-421] [PMID: 21961726]
[http://dx.doi.org/10.1093/carcin/bgi269] [PMID: 16299383]
[http://dx.doi.org/10.1038/35094067] [PMID: 11900252]
[http://dx.doi.org/10.1002/ibd.20129] [PMID: 17343284]
[http://dx.doi.org/10.1073/pnas.0903499106] [PMID: 19443690]
[http://dx.doi.org/10.1016/S0006-291X(02)02564-0] [PMID: 12419319]
[http://dx.doi.org/10.1016/j.bbrc.2011.09.034] [PMID: 21945442]
[http://dx.doi.org/10.3390/ijms17111860] [PMID: 27834811]
[http://dx.doi.org/10.1016/j.peptides.2012.09.024] [PMID: 23026680]
[http://dx.doi.org/10.1007/s11010-013-1920-3] [PMID: 24357116]
[http://dx.doi.org/10.1111/jcmm.15752] [PMID: 33325631]
[http://dx.doi.org/10.1002/(SICI)1097-0215(19990719)82:2<213:AID-IJC11>3.0.CO;2-8] [PMID: 10389755]
[http://dx.doi.org/10.1016/S0960-7404(96)80028-4] [PMID: 9129137]