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周围神经与胰腺癌细胞之间的代谢交流机制

田庚洲 邹雷

引用本文:
Citation:

周围神经与胰腺癌细胞之间的代谢交流机制

DOI: 10.3969/j.issn.1001-5256.2022.12.040
基金项目: 

昆医联合专项-杰出青年培育项目 202101AY070001-032;

基础研究专项-面上项目 202001AT070018

利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:田庚洲、邹雷参与起草论文,并修改文章关键内容。
详细信息
    通信作者:

    邹雷, zl_8082@126.com

Research advances in the mechanism of metabolic communication between peripheral nerves and pancreatic cancer cells

Research funding: 

Kunming Medical Association Special Project - Outstanding Youth Cultivation Project 202101AY070001-032;

Special Project of Basic Research - General Project 202001AT070018

More Information
    Corresponding author: ZOU Lei, zl_8082@126.com (ORCID: 0000-0001-7515-9073)
  • 摘要: 肿瘤微环境中各种物质代谢相互联系,代谢信号通路相互作用形成了复杂的代谢网络,共同维持肿瘤微环境的稳态。周围神经由核周体和神经纤维构成的神经干、神经丛、神经节及神经终末装置等组成,在胰腺癌的发展中发挥着关键作用。而目前周围神经与胰腺癌细胞之间代谢交流作用机制的研究相对较少。本文回顾近年来的研究,分别从周围神经和胰腺癌细胞的角度总结了氨基酸、神经递质、神经营养因子等在胰腺癌发展中的作用,认为探讨周围神经和胰腺癌细胞之间的代谢交流机制对发现新的胰腺癌治疗相关靶点有着重要作用。

     

  • 图  1  肿瘤微环境中神经细胞与胰腺癌细胞代谢交流示意图

    注:P物质,十一氨基酸多肽;N受体,烟碱型受体;M受体,毒蕈碱型受体;SEMA3D蛋白,轴突引导因子。实线,有促进作用;虚线,有抑制作用。

    Figure  1.  Metabolic Communication between nerve cells and pancreatic cancer cells in tumor microenvironment

  • [1] SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30. DOI: 10.3322/caac.21590.
    [2] DEMIR IE, CEYHAN GO, LIEBL F, et al. Neural invasion in pancreatic cancer: the past, present and future[J]. Cancers (Basel), 2010, 2(3): 1513-1527. DOI: 10.3390/cancers2031513.
    [3] CARRER A, TREFELY S, ZHAO S, et al. Acetyl-CoA metabolism supports multistep pancreatic tumorigenesis[J]. Cancer Discov, 2019, 9(3): 416-435. DOI: 10.1158/2159-8290.CD-18-0567.
    [4] STYLIANOPOULOS T, MARTIN JD, CHAUHAN VP, et al. Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors[J]. Proc Natl Acad Sci U S A, 2012, 109(38): 15101-15108. DOI: 10.1073/pnas.1213353109.
    [5] HALBROOK CJ, LYSSIOTIS CA. Employing metabolism to improve the diagnosis and treatment of pancreatic cancer[J]. Cancer Cell, 2017, 31(1): 5-19. DOI: 10.1016/j.ccell.2016.12.006.
    [6] ENTSCHLADEN F, PALM D, NIGGEMANN B, et al. The cancer's nervous tooth: Considering the neuronal crosstalk within tumors[J]. Semin Cancer Biol, 2008, 18(3): 171-175. DOI: 10.1016/j.semcancer.2007.12.004.
    [7] SALOMAN JL, ALBERS KM, LI D, et al. Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer[J]. Proc Natl Acad Sci U S A, 2016, 113(11): 3078-3083. DOI: 10.1073/pnas.1512603113.
    [8] SULLIVAN MR, MATTAINI KR, DENNSTEDT EA, et al. Increased serine synthesis provides an advantage for tumors arising in tissues where serine levels are limiting[J]. Cell Metab, 2019, 29(6): 1410-1421.e4. DOI: 10.1016/j.cmet.2019.02.015.
    [9] YANG MW, TAO LY, JIANG YS, et al. Perineural invasion reprograms the immune microenvironment through cholinergic signaling in pancreatic ductal adenocarcinoma[J]. Cancer Res, 2020, 80(10): 1991-2003. DOI: 10.1158/0008-5472.CAN-19-2689.
    [10] RENZ BW, TAKAHASHI R, TANAKA T, et al. β2 Adrenergic-neurotrophin feedforward loop promotes pancreatic cancer[J]. Cancer Cell, 2018, 33(1): 75-90.e7. DOI: 10.1016/j.ccell.2017.11.007.
    [11] HUANG C, LI Y, GUO Y, et al. MMP1/PAR1/SP/NK1R paracrine loop modulates early perineural invasion of pancreatic cancer cells[J]. Theranostics, 2018, 8(11): 3074-3086. DOI: 10.7150/thno.24281.
    [12] FRANCESCONE R, BARBOSA VENDRAMINI-COSTA D, FRANCO-BARRAZA J, et al. Netrin G1 promotes pancreatic tumorigenesis through cancer-associated fibroblast-driven nutritional support and immunosuppression[J]. Cancer Discov, 2021, 11(2): 446-479. DOI: 10.1158/2159-8290.CD-20-0775.
    [13] KAMPHORST JJ, NOFAL M, COMMISSO C, et al. Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein[J]. Cancer Res, 2015, 75(3): 544-553. DOI: 10.1158/0008-5472.CAN-14-2211.
    [14] MADDOCKS OD, BERKERS CR, MASON SM, et al. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells[J]. Nature, 2013, 493(7433): 542-546. DOI: 10.1038/nature11743.
    [15] SAMANTA D, PARK Y, ANDRABI SA, et al. PHGDH expression is required for mitochondrial redox homeostasis, breast cancer stem cell maintenance, and lung metastasis[J]. Cancer Res, 2016, 76(15): 4430-4442. DOI: 10.1158/0008-5472.CAN-16-0530.
    [16] BAO XR, ONG SE, GOLDBERGER O, et al. Mitochondrial dysfunction remodels one-carbon metabolism in human cells[J]. Elife, 2016, 5: e10575. DOI: 10.7554/eLife.10575.
    [17] BEN-SAHRA I, HOXHAJ G, RICOULT S, et al. mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle[J]. Science, 2016, 351(6274): 728-733. DOI: 10.1126/science.aad0489.
    [18] BANH RS, BIANCUR DE, YAMAMOTO K, et al. Neurons release serine to support mrna translation in pancreatic cancer[J]. Cell, 2020, 183(5): 1202-1218.e25. DOI: 10.1016/j.cell.2020.10.016.
    [19] SONG YS, LEE HJ, PROSSELKOV P, et al. Trans-induced cis interaction in the tripartite NGL-1, netrin-G1 and LAR adhesion complex promotes development of excitatory synapses[J]. J Cell Sci, 2013, 126(Pt 21): 4926-4938. DOI: 10.1242/jcs.129718.
    [20] NISHI K, SUZUKI M, YAMAMOTO N, et al. Glutamine deprivation enhances acetyl-coa carboxylase inhibitor-induced death of human pancreatic cancer cells[J]. Anticancer Res, 2018, 38(12): 6683-6689. DOI: 10.21873/anticanres.13036.
    [21] de COUCK M, MARÉCHAL R, MOORTHAMERS S, et al. Vagal nerve activity predicts overall survival in metastatic pancreatic cancer, mediated by inflammation[J]. Cancer Epidemiol, 2016, 40: 47-51. DOI: 10.1016/j.canep.2015.11.007.
    [22] RENZ BW, TANAKA T, SUNAGAWA M, et al. Cholinergic signaling via muscarinic receptors directly and indirectly suppresses pancreatic tumorigenesis and cancer stemness[J]. Cancer Discov, 2018, 8(11): 1458-1473. DOI: 10.1158/2159-8290.CD-18-0046.
    [23] WEDDLE DL, TITHOFF P, WILLIAMS M, et al. Beta-adrenergic growth regulation of human cancer cell lines derived from pancreatic ductal carcinomas[J]. Carcinogenesis, 2001, 22(3): 473-479. DOI: 10.1093/carcin/22.3.473.
    [24] KIM-FUCHS C, LE CP, PIMENTEL MA, et al. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment[J]. Brain Behav Immun, 2014, 40: 40-47. DOI: 10.1016/j.bbi.2014.02.019.
    [25] ZAHALKA AH, ARNAL-ESTAPÉ A, MARYANOVICH M, et al. Adrenergic nerves activate an angio-metabolic switch in prostate cancer[J]. Science, 2017, 358(6361): 321-326. DOI: 10.1126/science.aah5072.
    [26] PU J, ZHANG X, LUO H, et al. Adrenaline promotes epithelial-to-mesenchymal transition via HuR-TGFβ regulatory axis in pancreatic cancer cells and the implication in cancer prognosis[J]. Biochem Biophys Res Commun, 2017, 493(3): 1273-1279. DOI: 10.1016/j.bbrc.2017.09.146.
    [27] XIAO MB, JIN DD, JIAO YJ, et al. β2-AR regulates the expression of AKR1B1 in human pancreatic cancer cells and promotes their proliferation via the ERK1/2 pathway[J]. Mol Biol Rep, 2018, 45(6): 1863-1871. DOI: 10.1007/s11033-018-4332-3.
    [28] MUÑOZ M, ROSSO M. The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug[J]. Invest New Drugs, 2010, 28(2): 187-193. DOI: 10.1007/s10637-009-9218-8.
    [29] HENNIG IM, LAISSUE JA, HORISBERGER U, et al. Substance-P receptors in human primary neoplasms: tumoral and vascular localization[J]. Int J Cancer, 1995, 61(6): 786-792. DOI: 10.1002/ijc.2910610608.
    [30] MUÑOZ M, ROSSO M, COVEÑAS R. The NK-1 receptor: a new target in cancer therapy[J]. Curr Drug Targets, 2011, 12(6): 909-921. DOI: 10.2174/138945011795528796.
    [31] MEDRANO S, GRUENSTEIN E, DIMLICH RV. Substance P receptors on human astrocytoma cells are linked to glycogen breakdown[J]. Neurosci Lett, 1994, 167(1-2): 14-18. DOI: 10.1016/0304-3940(94)91017-0.
    [32] LI X, MA G, MA Q, et al. Neurotransmitter substance P mediates pancreatic cancer perineural invasion via NK-1R in cancer cells[J]. Mol Cancer Res, 2013, 11(3): 294-302. DOI: 10.1158/1541-7786.MCR-12-0609.
    [33] HESSMANN E, BUCHHOLZ SM, DEMIR IE, et al. Microenvironmental determinants of pancreatic cancer[J]. Physiol Rev, 2020, 100(4): 1707-1751. DOI: 10.1152/physrev.00042.2019.
    [34] DEMIR IE, FRIESS H, CEYHAN GO. Nerve-cancer interactions in the stromal biology of pancreatic cancer[J]. Front Physiol, 2012, 3: 97. DOI: 10.3389/fphys.2012.00097.
    [35] MASTRANTONIO R, YOU H, TAMAGNONE L. Semaphorins as emerging clinical biomarkers and therapeutic targets in cancer[J]. Theranostics, 2021, 11(7): 3262-3277. DOI: 10.7150/thno.54023.
    [36] FOLEY K, RUCKI AA, XIAO Q, et al. Semaphorin 3D autocrine signaling mediates the metastatic role of annexin A2 in pancreatic cancer[J]. Sci Signal, 2015, 8(388): ra77. DOI: 10.1126/scisignal.aaa5823.
    [37] JURCAK NR, RUCKI AA, MUTH S, et al. Axon guidance molecules promote perineural invasion and metastasis of orthotopic pancreatic tumors in mice[J]. Gastroenterology, 2019, 157(3): 838-850.e6. DOI: 10.1053/j.gastro.2019.05.065.
    [38] CEYHAN GO, SCHÄFER KH, KERSCHER AG, et al. Nerve growth factor and artemin are paracrine mediators of pancreatic neuropathy in pancreatic adenocarcinoma[J]. Ann Surg, 2010, 251(5): 923-931. DOI: 10.1097/SLA.0b013e3181d974d4.
    [39] ITO Y, OKADA Y, SATO M, et al. Expression of glial cell line-derived neurotrophic factor family members and their receptors in pancreatic cancers[J]. Surgery, 2005, 138(4): 788-794. DOI: 10.1016/j.surg.2005.07.007.
    [40] GIL Z, CAVEL O, KELLY K, et al. Paracrine regulation of pancreatic cancer cell invasion by peripheral nerves[J]. J Natl Cancer Inst, 2010, 102(2): 107-118. DOI: 10.1093/jnci/djp456.
    [41] CAVEL O, SHOMRON O, SHABTAY A, et al. Endoneurial macrophages induce perineural invasion of pancreatic cancer cells by secretion of GDNF and activation of RET tyrosine kinase receptor[J]. Cancer Res, 2012, 72(22): 5733-5743. DOI: 10.1158/0008-5472.CAN-12-0764.
    [42] ZHANG JF, TAO LY, YANG MW, et al. CD74 promotes perineural invasion of cancer cells and mediates neuroplasticity via the AKT/EGR-1/GDNF axis in pancreatic ductal adenocarcinoma[J]. Cancer Lett, 2021, 508: 47-58. DOI: 10.1016/j.canlet.2021.03.016.
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  • 收稿日期:  2022-03-30
  • 录用日期:  2022-05-19
  • 出版日期:  2022-12-20
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