A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
10 Jan 2024
10 Jan 2024
Historique:
received:
13
07
2023
accepted:
05
12
2023
revised:
27
11
2023
medline:
11
1
2024
pubmed:
11
1
2024
entrez:
10
1
2024
Statut:
aheadofprint
Résumé
In this study we conducted the first investigation to assess the efficacy of a novel therapeutic antibody developed to target annexin-A1 (ANXA1). ANXA1 is an immunomodulatory protein which has been shown to be overexpressed in, and promote the development and progression of, several cancer types. In particular, high ANXA1 expression levels correlate with poorer overall survival in pancreatic and triple-negative breast cancers, two cancers with considerable unmet clinical need. MDX-124 is a humanised IgG1 monoclonal antibody which specifically binds to ANXA1 disrupting its interaction with formyl peptide receptors 1 and 2 (FPR1/2). Here we show that MDX-124 significantly reduced proliferation (p < 0.013) in a dose-dependent manner across a panel of human cancer cell lines expressing ANXA1. The anti-proliferative effect of MDX-124 is instigated by arresting cell cycle progression with cancer cells accumulating in the G
Identifiants
pubmed: 38200229
doi: 10.1038/s41388-023-02919-9
pii: 10.1038/s41388-023-02919-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Gerke V, Moss SE. Annexins: from structure to function. Physiol Rev. 2002;82:331–71.
doi: 10.1152/physrev.00030.2001
pubmed: 11917092
Perretti M, D’Acquisto F. Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol. 2009;9:62–70.
doi: 10.1038/nri2470
pubmed: 19104500
Williams SL, Milne IR, Bagley CJ, Gamble JR, Vadas MA, Pitson SM, et al. A proinflammatory role for proteolytically cleaved annexin A1 in neutrophil transendothelial migration. J Immunol. 2010;185:3057–63.
doi: 10.4049/jimmunol.1000119
pubmed: 20679535
D’Acquisto F, Piras G, Rattazzi L. Pro-inflammatory and pathogenic properties of annexin-A1: the whole is greater than the sum of its parts. Biochem Pharm. 2013;85:1213–8.
doi: 10.1016/j.bcp.2013.02.011
pubmed: 23435354
Sugimoto MA, Vago JP, Teixeira MM, Sousa LP. Annexin A1 and the resolution of inflammation: modulation of neutrophil recruitment, apoptosis, and clearance. J Immunol Res. 2016;2016:8239258.
doi: 10.1155/2016/8239258
pubmed: 26885535
pmcid: 4738713
Araújo TG, Mota STS, Ferreira HSV, Ribeiro MA, Goulart LR, Vecchi L. Annexin a1 as a regulator of immune response in cancer. Cells. 2021;10:2245.
doi: 10.3390/cells10092245
pubmed: 34571894
pmcid: 8464935
Boudhraa Z, Bouchon B, Viallard C, D’Incan M, Degoul F. Annexin A1 localization and its relevance to cancer. Clin Sci. 2016;130:205–20.
doi: 10.1042/CS20150415
Bai XF, Ni XG, Zhao P, Liu SM, Wang HX, Guo B, et al. Overexpression of annexin 1 in pancreatic cancer and its clinical significance. World J Gastroenterol. 2004;10:1466–70.
doi: 10.3748/wjg.v10.i10.1466
pubmed: 15133855
pmcid: 4656286
Ydy LRA, do Espírito Santo GF, de Menezes I, Martins MS, Ignotti E, Damazo AS. Study of the annexin A1 and its associations with carcinoembryonic antigen and mismatch repair proteins in colorectal cancer. J Gastrointest Cancer. 2016;47:61–8.
doi: 10.1007/s12029-015-9791-3
pubmed: 26687139
Biaoxue R, Zhao C, Liu H, Ming Z, Cai X, Gao W, et al. Elevated serum annexin A1 as potential diagnostic marker for lung cancer: a retrospective case-control study. Am J Transl Res. 2014;6:558–69.
Cheng TY, Wu MS, Lin JT, Lin MT, Shun CT, Huang HY, et al. Annexin A1 is associated with gastric cancer survival and promotes gastric cancer cell invasiveness through the formyl peptide receptor/extracellular signal-regulated kinase/integrin beta-1-binding protein 1 pathway. Cancer. 2012;118:5757–67.
doi: 10.1002/cncr.27565
pubmed: 22736399
Liu YF, Zhang PF, Li MY, Li QQ, Chen ZC. Identification of annexin A1 as a proinvasive and prognostic factor for lung adenocarcinoma. Clin Exp Metastasis. 2011;28:413–25.
doi: 10.1007/s10585-011-9380-1
pubmed: 21365324
Yom CK, Han W, Kim SW, Kim HS, Shin HC, Chang JN, et al. Clinical signifcance of annexin A1 expression in breast cancer. J Breast Cancer. 2011;14:262–8.
doi: 10.4048/jbc.2011.14.4.262
pubmed: 22323911
pmcid: 3268921
Bhardwaj A, Ganesan N, Tachibana K, Rajapakshe K, Albarracin CT, Gunaratne PH, et al. Annexin A1 preferentially predicts poor prognosis of basal-like breast cancer patients by activating mTOR-S6 signaling. PLoS ONE. 2015;10:1–19.
doi: 10.1371/journal.pone.0127678
Gibbs LD, Vishwanatha JK. Prognostic impact of AnxA1 and AnxA2 gene expression in triple-negative breast cancer. Oncotarget. 2018;9:2697–704.
doi: 10.18632/oncotarget.23627
pubmed: 29416802
Vecchi L, Alves Pereira Zóia M, Goss Santos T, de Oliveira Beserra A, Colaço Ramos CM, França Matias Colombo B, et al. Inhibition of the AnxA1/FPR1 autocrine axis reduces MDA-MB-231 breast cancer cell growth and aggressiveness in vitro and in vivo. Biochim Biophys Acta Mol Cell Res. 2018;1865:1368–82.
doi: 10.1016/j.bbamcr.2018.06.010
pubmed: 29932988
Yi M, Schnitzer JE. Impaired tumor growth, metastasis, angiogenesis and wound healing in annexin A1-null mice. Proc Natl Acad Sci USA. 2009;106:17886–91.
doi: 10.1073/pnas.0901324106
pubmed: 19805119
pmcid: 2764877
Belvedere R, Bizzarro V, Popolo A, Dal Piaz F, Vasaturo M, Picardi P, et al. Role of intracellular and extracellular annexin A1 in migration and invasion of human pancreatic carcinoma cells. BMC Cancer. 2014;14:1–15.
doi: 10.1186/1471-2407-14-961
Onozawa H, Saito M, Saito K, Kanke Y, Watanabe Y, Hayase S, et al. Annexin A1 is involved in resistance to 5-FU in colon cancer cells. Oncol Rep. 2017;37:235–40.
doi: 10.3892/or.2016.5234
pubmed: 27840982
Bai F, Zhang P, Fu Y, Chen H, Zhang M, Huang Q, et al. Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer. J Immunother Cancer. 2020;8:1–9.
doi: 10.1136/jitc-2019-000169
Moraes LA, Kar S, Foo SL, Gu T, Toh YQ, Ampomah PB, et al. Annexin-A1 enhances breast cancer growth and migration by promoting alternative macrophage polarization in the tumour microenvironment. Sci Rep. 2017;7:1–12.
doi: 10.1038/s41598-017-17622-5
Weyd H, Abeler-Dörner L, Linke B, Mahr A, Jahndel V, Pfrang S, et al. Annexin A1 on the surface of early apoptotic cells suppresses CD8+ T cell immunity. PLoS ONE. 2013;8:e62449.
doi: 10.1371/journal.pone.0062449
pubmed: 23638088
pmcid: 3640057
Novizio N, Belvedere R, Pessolano E, Tosco A, Porta A, Perretti M, et al. Annexin A1 released in extracellular vesicles by pancreatic cancer cells activates components of the tumor microenvironment, through interaction with the formyl-peptide receptors. Cells. 2020;9:1–18.
doi: 10.3390/cells9122719
Geary LA, Nash KA, Adisetiyo H, Liang M, Liao CP, Jeong JH, et al. CAF-secreted annexin A1 induces prostate cancer cells to gain stem cell-like features. Mol Cancer Res. 2014;12:607–21.
doi: 10.1158/1541-7786.MCR-13-0469
pubmed: 24464914
pmcid: 3989391
Wang LD, Yang YH, Liu Y, Song HT, Zhang LY, Li PL. Decreased expression of annexin A1 during the progression of cervical neoplasia. J Int Med Res. 2008;36:665–72.
doi: 10.1177/147323000803600407
pubmed: 18652761
Petrella A, Festa M, Ercolino SF, Zerilli M, Stassi G, Solito E, et al. Annexin-1 downregulation in thyroid cancer correlates to the degree of tumor differentiation. Cancer Biol Ther. 2006;5:643–7.
doi: 10.4161/cbt.5.6.2700
pubmed: 16627980
Shen D, Nooraie F, Elshimali Y, Lonsberry V, He J, Bose S, et al. Decreased expression of annexin A1 is correlated with breast cancer development and progression as determined by a tissue microarray analysis. Hum Pathol. 2006;37:1583–91.
doi: 10.1016/j.humpath.2006.06.001
pubmed: 16949910
Fu Z, Zhang S, Wang B, Huang W, Zheng L, Cheng A. Annexin A1: a double-edged sword as novel cancer biomarker. Clin Chim Acta. 2020;504:36–42.
doi: 10.1016/j.cca.2020.01.022
pubmed: 32006544
Gramlich M, Hays HCW, Crichton S, Kaiser PD, Heine A, Schneiderhan-Marra N, et al. HDX-MS for epitope characterization of a therapeutic antibody candidate on the calcium-binding protein annexin-A1. Antibodies. 2021;10:11.
doi: 10.3390/antib10010011
pubmed: 33808657
pmcid: 8006148
Gavins FNE, Hickey MJ. Annexin A1 and the regulation of innate and adaptive immunity. Front Immunol. 2012;3:354.
doi: 10.3389/fimmu.2012.00354
pubmed: 23230437
pmcid: 3515881
Kelly L, McGrath S, Rodgers L, McCall K, Tulunay Virlan A, Dempsey F, et al. Annexin‐A1: the culprit or the solution? Immunology. 2022;166:2–16.
doi: 10.1111/imm.13455
pubmed: 35146757
Vecchi L, Mota STS, Zóia MAP, Martins IC, de Souza JB, Santos TG, et al. Interleukin-6 signaling in triple negative breast cancer cells elicits the annexin A1/formyl peptide receptor 1 axis and affects the tumor microenvironment. Cells. 2022;11(May):1705.
doi: 10.3390/cells11101705
pubmed: 35626741
pmcid: 9139391
Khau T, Langenbach SY, Schuliga M, Harris T, Johnstone CN, Anderson RL, et al. Annexin-1 signals mitogen-stimulated breast tumor cell proliferation by activation of the formyl peptide receptors (FPRs) 1 and 2. FASEB J. 2011;25:483–96.
doi: 10.1096/fj.09-154096
pubmed: 20930115
Johnstone CN, Tu Y, Langenbach S, Baloyan D, Pattison AD, Lock P, et al. Annexin a1 is required for efficient tumor initiation and cancer stem cell maintenance in a model of human breast cancer. Cancers. 2021;13:1–27.
doi: 10.3390/cancers13051154
Liu QH, Shi ML, Bai J, Zheng JN. Identification of ANXA1 as a lymphatic metastasis and poor prognostic factor in pancreatic ductal adenocarcinoma. Asian Pac J Cancer Prev. 2015;16:2719–24.
doi: 10.7314/APJCP.2015.16.7.2719
pubmed: 25854353
Rubinstein MR, Baik JE, Lagana SM, Han RP, Raab WJ, Sahoo D, et al. Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β‐catenin modulator Annexin A1. EMBO Rep. 2019;20:e47638.
doi: 10.15252/embr.201847638
pubmed: 30833345
pmcid: 6446206
Allen KL, Cann J, Zhao W, Peterson N, Lazzaro M, Zhong H, et al. Upregulation of annexin A1 protein expression in the intratumoral vasculature of human non–small-cell lung carcinoma and rodent tumor models. PLoS ONE. 2020;15:1–20.
doi: 10.1371/journal.pone.0234268
De Graauw M, Van Miltenburg MH, Schmidt MK, Pont C, Lalai R, Kartopawiro J, et al. Annexin A1 regulates TGF-β signaling and promotes metastasis formation of basal-like breast cancer cells. Proc Natl Acad Sci USA. 2010;107:6340–5.
doi: 10.1073/pnas.0913360107
pubmed: 20308542
pmcid: 2852023
Plumb JA. Cell Sensitivity Assays: The MTT assay. In: Cancer cell culture. New Jersey: Humana Press; 2004. p. 165–70.
Parris CN, Adam Zahir S, Al-Ali H, Bourton EC, Plowman C, Plowman PN. Enhanced γ-H2AX DNA damage foci detection using multimagnification and extended depth of field in imaging flow cytometry. Cytom Part A. 2015;87:717–23.
doi: 10.1002/cyto.a.22697