|Table of Contents|

Research progress on the effect of adrenomedullin on tumorigenesis and development

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 21
Page:
4067-4072
Research Field:
Publishing date:

Info

Title:
Research progress on the effect of adrenomedullin on tumorigenesis and development
Author(s):
PAN MeizhuZHANG Yi
Department of Gynecology,the First Hospital of China Medical University,Liaoning Shenyang 110001,China.
Keywords:
adrenomedullinphysiological functionthe occurrence and development of tumorstumor microenvironment
PACS:
R730
DOI:
10.3969/j.issn.1672-4992.2023.21.031
Abstract:
Adrenomedullin(ADM) is a antihypertensive and vasodilator peptide belonging to calcitonin gene-related peptide family.It does not cause cancer by itself,but it can promote its progress through different mechanisms.In this review,the physiological function of ADM,its role in the occurrence and development of tumor,the dynamic and diverse immune components in tumor microenvironment(TME) and the regulatory effect of ADM on TME were discussed.This paper expounds the important role of ADM in inducing tumor angiogenesis,promoting the proliferation,metastasis and invasion of tumor cells,and resisting apoptosis.ADM has been proved to be highly expressed in various tumor tissues and cells,and it is a key factor in promoting tumor progression.It not only affects the malignant growth process of solid tumor cells,but also affects the immune cells and matrix in TME,creating a microenvironment suitable for the survival of tumor cells and promoting the occurrence and development of tumor.

References:

[1] FISCHER JP,ELS-HEINDL S,BECK-SICKINGER AG.Adrenomedullin-current perspective on a peptide hormone with significant therapeutic potential[J].Peptides,2020,131:170347.
[2] KITAMURA K,SAKATA J,KANGAWA K,et al.Cloning and characterization of cDNA encoding a precursor for human adrenomedullin[J].Biochem Biophys Res Commun,1993,194(2):720-725.
[3] LARRAYOZ IM,MARTINEZ-HERRERO S,GARCIA-SANMARTIN J,et al.Adrenomedullin and tumour microenvironment[J].J Transl Med,2014,12:339.
[4] LI S.The neuropeptide adrenomedullin promoted the progression of head and neck squamous carcinoma by negatively regulating tumour immunity[J].Int J Cancer Res Ther,2022,7(4):183-199.
[5] GEVEN C,KOX M,PICKKERS P.Adrenomedullin and adrenomedullin-targeted therapy as treatment strategies relevant for sepsis[J].Front Immunol,2018,9:292.
[6] SHINDO T,TANAKA M,KAMIYOSHI A,et al.Regulation of cardiovascular development and homeostasis by the adrenomedullin-RAMP system[J].Peptides,2019,111:55-61.
[7] TSURUDA T,KATO J,KUWASAKO K,et al.Adrenomedullin:continuing to explore cardioprotection[J].Peptides,2019,111:47-54.
[8] DAGA MK,KUMAR L,MAWARI G,et al.Adrenomedullin and its possible role in improved survival in female patients with sepsis:a study in the south east asian region[J].Indian J Crit Care Med,2020,24(12):1180-1184.
[9] LI FJ,ZHENG SR,WANG DM.Adrenomedullin:an important participant in neurological diseases[J].Neural Regen Res,2020,15(7):1199-1207.
[10] MARTINEZ-HERRERO S,MARTINEZ A.Adrenomedullin:not just another gastrointestinal peptide[J].Biomolecules,2022,12(2):156.
[11] KATO J,KAWAGOE Y,JIANG D,et al.Plasma adrenomedullin level and year-by-year variability of body mass index in the general population[J].Peptides,2021,142:170567.
[12] DONG Y,RUANO SH,MISHRA A,et al.Adrenomedullin and its receptors are expressed in mouse pancreatic β-cells and suppresses insulin synthesis and secretion[J].PLoS One,2022,17(3):e265890.
[13] 韩晓鹏.肾上腺髓质素的研究进展[J].中山大学学报(医学科学版),2009,30(4S):275-279. HAN XP.Advances in research on adrenomedullin[J].Journal of Sun Yat-Sen University(Medical Sciences),2009,30(4S):275-279.
[14] NISHIKIMI T.Adrenomedullin in the kidney-renal physiological and pathophysiological roles[J].Curr Med Chem,2007,14(15):1689-1699.
[15] KARLI P,BILDIRCIN FD,OZDEMIR AZ,et al.Higher adrenomedullin levels during implantation are associated with successful pregnancy[J].Future Sci OA,2020,6(2):FSO453.
[16]] 郝淑玲,于忠和.肾上腺髓质素与肺癌关系的研究进展[J].中华肿瘤防治杂志,2010,17(09):716-719. HAO SL,YU ZH.Role of adrenomedullin in pulmonary tumor[J].Chinese Journal of Cancer Prevention and Treatment,2010,17(09):716-719.
[17] GREILLIER L,TOUNSI A,BERENGUER-DAIZE C,et al.Functional analysis of the adrenomedullin pathway in malignant pleural mesothelioma[J].J Thorac Oncol,2016,11(1):94-107.
[18] PAREM,DARINI CY,YAO X,et al.Breast cancer mammospheres secrete Adrenomedullin to induce lipolysis and browning of adjacent adipocytes[J].BMC Cancer,2020,20(1):784.
[19] BIGOS KJA.The role of adrenomedullin signalling in pancreatic cancer[D].Sheffield:University of Sheffield,2021.
[20] LI M,HONG LI,LIAO M,et al.Expression and clinical significance of focal adhesion kinase and adrenomedullin in epithelial ovarian cancer[J].Oncol Lett,2015,10(2):1003-1007.
[21] BOZKURT KK,YALCIN Y,ERDEMOCLU E,et al.The role of immunohistochemical adrenomedullin and Bcl-2 expression in development of type-1 endometrial adenocarcinoma[J].Pathol Res Pract,2016,212(5):450-455.
[22] CABIATI M,GAGGINI M,DE SIMONE P,et al.Expression profile of adrenomedullin and its specific receptors in liver tissues from patients with hepatocellular carcinoma and in tumorigenic cell line-secreted extracellular vesicles[J].Pathol Res Pract,2023,243:154383.
[23] BRITTEN JL,MALIK M,DEANGELIS A.HIF1-alpha induced adrenomedullin expression supports angiogenesis in 3d leiomyoma xenografts[J].Fertil Steril,2020,114(3):e445.
[24] 李曼红,曾庆纯.肾上腺髓质素与微血管密度在子宫颈癌中的表达意义研究[J].中国实用医药,2015,10(12):58-59. LI MH,ZENG QC.Research of expression significance of adrenomedullin and microvessel density in cervical cancer[J].China Practical Medicine,2015,10(12):58-59.
[25] LU XQ,JI CX,QIAO FH.Expression of human adrenomedullin gene in gastric adenocarcinoma and construction and identification of adrenomedullin overexpression vector and adrenomedullin-shRNA vector[J].Tumor Microenvironment Research,2020,2(3):71-78.
[26] UDONO T,TOTSUNE K,TAKAHASHI K,et al.Increased expression of adrenomedullin mRNA in the tissues of intraocular and orbital tumors[J].Am J Ophthalmol,2000,129(4):555-556.
[27] BENYAHIA Z,GAUDY-MARQUESTE C,BERENGUER-DAIZE C,et al.Adrenomedullin secreted by melanoma cells promotes melanoma tumor growth through angiogenesis and lymphangiogenesis[J].Cancers,2022,14(23):5909.
[28] CHEN P,HUANG Y,BONG R,et al.Tumor-associated macrophages promote angiogenesis and melanoma growth via adrenomedullin in a paracrine and autocrine manner[J].Clin Cancer Res,2011,17(23):7230-7239.
[29] MORIYAMA T,OTANI T,MARUO T.Expression of adrenomedullin by human placental cytotrophoblasts and choriocarcinoma JAr cells[J].J Clin Endocrinol Metab,2001,86(8):3958-3961.
[30] ROCCHI P,BOUDOURESQUE F,ZAMORA AJ,et al.Expression of adrenomedullin and peptide amidation activity in human prostate cancer and in human prostate cancer cell lines[J].Cancer Res,2001,61(3):1196-1206.
[31] HE Z,CHENG M,HU J,et al.miR-1297 sensitizes glioma cells to temozolomide(TMZ)treatment through targeting adrenomedullin(ADM)[J].J Transl Med,2022,20(1):443.
[32] 李锁南.肾上腺髓质素和CGRP在垂体腺瘤与非肿瘤性脑垂体中的表达及其意义[D].长沙:中南大学,2008. LI SN.Adrenomedullin and CGRP expression and their relationship in pituitary adenomas and nontumoral adenohypophyses[D].Changsha:Central South University,2008.
[33] MAIA LL,PETERLE GT,DOS SANTOS M,et al.JMJD1A,H3K9me1,H3K9me2 and ADM expression as prognostic markers in oral and oropharyngeal squamous cell carcinoma[J].PLoS One,2018,13(3):e194884.
[34] 戴星,杨康平,尹战海,等.肾上腺髓质素在人骨肉瘤组织中的表达[J].山西医科大学学报,2019,50(09):1218-1223. DAI X,YANG KP,YIN ZH,et al.Expression of adrenomedullin in human osteosarcoma[J].Journal of Shanxi Medical University,2019,50(09):1218-1223.
[35] XU M,QI F,ZHANG S,et al.Adrenomedullin promotes the growth of pancreatic ductal adenocarcinoma through recruitment of myelomonocytic cells[J].Oncotarget,2016,7(34):55043-55056.
[36] IMAI H,OHIKE N,NOROSE T,et al.Involvement of adrenomedullin expression in tumor cells and stroma in the development of diabetes in pancreatic cancer patients[J].Showa Univ J Med Sci,2018,30(3):341-349.
[37] SAGAR G,SAH RP,JAVEED N,et al.Pathogenesis of pancreatic cancer exosome-induced lipolysis in adipose tissue[J].Gut,2016,65(7):1165-1174.
[38] 陈国强,徐瑞华.肿瘤学 [M].5版,北京:人民卫生出版社,2020:4. CHEN GQ,XU RH.Oncology[M].5th Edition,Beijing:People's Medical Publishing House,2020:4.
[39] 贝格雷.肿瘤微环境[M].覃文新,樊嘉,译.杭州:浙江大学出版社,2013:1-672. REBECCA G BAGLEY.The tumor microenvironment[M].TANG WX,FAN J,Translate.Hang Zhou:Zhejiang University Press,2013:1-672.
[40] VAZQUEZ R,RIVEIRO ME,BERENGUER-DAIZE C,et al.Targeting adrenomedullin in oncology:a feasible strategy with potential as much more than an alternative anti-angiogenic therapy[J].Front Oncol,2021,10:589218.
[41] BENYAHIA Z,DUSSAULT N,CAYOL M,et al.Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion[J].Oncotarget,2017,8(9):15744-15762.
[42] YAO L,WANG Y,MA W,et al.Downregulation of adrenomedullin leads to the inhibition of the tumorigenesis via VEGF pathway in human and nude mice osteosarcoma models[J].Arch Med Res,2019,50(1):47-57.
[43] LI MY,ZHU XL,ZHAO BX,et al.Adrenomedullin alleviates the pyroptosis of Leydig cells by promoting autophagy via the ROS-AMPK-mTOR axis[J].Cell Death Dis,2019,10(7):489.
[44] NAKAYAMA A,ROQUID KA,IRING A,et al.Suppression of CCL2 angiocrine function by adrenomedullin promotes tumor growth[J].J Exp Med,2023,220(1):e20211628.
[45] OEHLER MK,NORBURY C,HAGUE S,et al.Adrenomedullin inhibits hypoxic cell death by upregulation of Bcl-2 in endometrial cancer cells:a possible promotion mechanism for tumour growth[J].Oncogene,2001,20(23):2937-2945.
[46] BERENGUER-DAIZE C,BOUDOURESQUE F,BASTIDE C,et al.Adrenomedullin blockade suppresses growth of human hormone-independent prostate tumor xenograft in mice[J].Clin Cancer Res,2013,19(22):6138-6150.
[47] NOUGUEREDE E,BERENGUER C,GARCIA S,et al.Expression of adrenomedullin in human colorectal tumors and its role in cell growth and invasion in vitro and in xenograft growth in vivo[J].Cancer Med,2013,2(2):196-207.
[48] LIU AG,ZHANG XZ,LI FB,et al.RNA interference targeting adrenomedullin induces apoptosis and reduces the growth of human bladder urothelial cell carcinoma[J].Med Oncol,2013,30(3):616.
[49] PANG X,SHANG H,DENG B,et al.The interaction of adrenomedullin and macrophages induces ovarian cancer cell migration via activation of RhoA signaling pathway[J].Int J Mol Sci,2013,14(2):2774-2787.
[50] DAI K,TANAKA M,KAMIYOSHI A,et al.Deficiency of the adrenomedullin-RAMP3 system suppresses metastasis through the modification of cancer-associated fibroblasts[J].Oncogene,2020,39(9):1914-1930.
[51] MIYASHITA-ISHIWATA M,EL SABEH M,RESCHKE LD,et al.Differential response to hypoxia in leiomyoma and myometrial cells[J].Life Sci,2022,290:120238.
[52] 张璐,方岳,牛继国,等.缺氧诱导因子-1与恶性肿瘤关系的研究进展[J].医学综述,2021,27(05):924-930. ZHANG L,FANG Y,NIU JG,et al.Research progress in relationship between hypoxia-inducible factor-1 and malignant tumors[J].Medical Recapitulate,2021,27(05):924-930.
[53] ZHANG Y,XU Y,MA J,et al.Adrenomedullin promotes angiogenesis in epithelial ovarian cancer through upregulating hypoxia-inducible factor-1α and vascular endothelial growth factor[J].Sci Rep,2017,7:40524.
[54] CHEN Q,CHEN P,PANG X,et al.Adrenomedullin up-regulates the expression of vascular endothelial growth factor in epithelial ovarian carcinoma cells via JNK/AP-1 pathway[J].Int J Gynecol Cancer,2015,25(6):953-960.
[55] GARAYOA M,MARTINEZ A,LEE S,et al.Hypoxia-inducible factor-1(HIF-1) up-regulates adrenomedullin expression in human tumor cell lines during oxygen deprivation:a possible promotion mechanism of carcinogenesis[J].Mol Endocrinol,2000,14(6):848-862.
[56] 张赟,王小凡.肿瘤微环境调控癌症发生发展的研究概述[J].中国科学:生命科学,2022,52(09):1377-1390. ZHANG Y,WANG XF.Microenvironmental regulation of tumor initiation and development [J].Scientia Sinica Vitae,2022,52(09):1377-1390.
[57] SIMONETTI G,ANGELI D,PETRACCI E,et al.Adrenomedullin expression characterizes leukemia stem cells and associates with an inflammatory signature in acute myeloid leukemia[J].Front Oncol,2021,11:684396.
[58] ZUDAIRE E,PORTAL-NUNEZ S,CUTTITTA F.The central role of adrenomedullin in host defense[J].J Leukoc Biol,2006,80(2):237-244.
[59] RAMACHANDRAN V,ARUMUGAM T,LANGLEY R,et al.The ADMR receptor mediates the effects of adrenomedullin on pancreatic cancer cells and on cells of the tumor microenvironment[J].PLoS One,2009,4(10):e7502.
[60] 陈玉乐,杨文杰,吕伟,等.肾上腺髓质素、受体活性调节蛋白2、3在膀胱癌的表达及意义[J].现代泌尿外科杂志,2019,24(12):1038-1041. CHEN YL,YANG WJ,LV W,et al.Expresions and significance of AM,RAMP2 and RAMP3 in bladder cancer[J].Journal of Modern Urology,2019,24(12):1038-1041.
[61] KELEG S,KAYED H,JIANG X,et al.Adrenomedullin is induced by hypoxia and enhances pancreatic cancer cell invasion[J].Int J Cancer,2007,121(1):21-32.
[62] ISHIKAWA T,CHEN J,WANG J,et al.Adrenomedullin antagonist suppresses in vivo growth of human pancreatic cancer cells in SCID mice by suppressing angiogenesis[J].Oncogene,2003,22(8):1238-1242.
[63] APONTE-LOPEZ A,MUNOZ-CRUZ S.Mast cells in the tumor microenvironment[J].Adv Exp Med Biol,2020,1273:159-173.
[64] LV YP,PENG LS,WANG QH,et al.Degranulation of mast cells induced by gastric cancer-derived adrenomedullin prompts gastric cancer progression[J].Cell Death Dis,2018,9(10):1034.
[65] 吕一品.肥大细胞在胃癌中的分布、应答调控及作用机制研究[D].重庆:中国人民解放军陆军军医大学,2019. LV YP.Distribution,functional immunoregulation and tumor-promoting effects of mast cells in gastric cancer[D].Chongqing:Army Medical University,2019.
[66] ZUDAIRE E,MARTINEZ A,GARAYOA M,et al.Adrenomedullin is a cross-talk molecule that regulates tumor and mast cell function during human carcinogenesis[J].Am J Pathol,2006,168(1):280-291.
[67] 杨黎,张毅.肿瘤相关巨噬细胞研究进展[J].中国免疫学杂志,2020,36(02):129-135. YANG L,ZHANG Y.Research progress on tumor-associated macrophages[J].Chinese Journal of Immunology,2020,36(02):129-135.
[68] 谢玙玙,段昕所.肿瘤微环境下巨噬细胞的极化和靶向治疗意义[J].华西医学,2021,36(05):679-685. XIE YY,DUAN XS.Significance of polarization and targeted therapy of macrophages in tumor microenvironment[J].West China Medical Journal,2021,36(05):679-685.
[69] LI C,XU X,WEI S,et al.Tumor-associated macrophages:potential therapeutic strategies and future prospects in cancer[J].J Immunother Cancer,2021,9(1):e001341.
[70] BARANELLO C,MARIANI M,ANDREOLI M,et al.Adrenomedullin in ovarian cancer:foe in vitro and friend in vivo[J].PLoS One,2012,7(7):e40678.
[71] GIVEL A,KIEFFER Y,SCHOLER-DAHIREL A,et al.miR200-regulated CXCL12β promotes fibroblast heterogeneity and immunosuppression in ovarian cancers[J].Nat Commun,2018,9(1):1056.
[72] ZHANG B,CHEN F,XU Q,et al.Revisiting ovarian cancer microenvironment:a friend or a foe[J].Protein Cell,2018,9(8):674-692.
[73] RODRIGUEZ GM,GALPIN KJC,MCCLOSKEY CW,et al.The tumor microenvironment of epithelial ovarian cancer and its influence on response to immunotherapy[J].Cancers,2018,10(8):242.
[74] LEUNG CS,YEUNG TL,YIP KP,et al.Cancer-associated fibroblasts regulate endothelial adhesion protein LPP to promote ovarian cancer chemoresistance[J].J Clin Invest,2018,128(2):589-606.
[75] REN Y,JIA HH,XU YQ,et al.Paracrine and epigenetic control of CAF-induced metastasis:the role of HOTAIR stimulated by TGF-ss1 secretion[J].Mol Cancer,2018,17(1):5.
[76] ZHANG D,LI L,JIANG H,et al.Tumor-stroma IL1beta-IRAK4 feedforward circuitry drives tumor fibrosis,chemoresistance,and poor prognosis in pancreatic cancer[J].Cancer Res,2018,78(7):1700-1712.

Memo

Memo:
国家卫生健康委医药卫生科技发展研究中心(编号:HDSL202003005);辽宁省应用基础研究计划(编号:2022JH2/101300039);辽宁省沈阳市科技计划(编号:22-321-33-08)
Last Update: 2023-09-28