Neutrophil Extracellular Trap-Associated CEACAM1 As a Putative Therapeutic Target to Prevent Metastatic Progression of Colon Carcinoma

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2020 Mar 15

PMID 32169849

Citations 46

Authors

Roni F Rayes

Phil Vourtzoumis

Marianne Bou Rjeily

Rashmi Seth

France Bourdeau

Betty Giannias

Julie Berube

Yu-Hwa Huang

Simon Rousseau

Sophie Camilleri-Broet

Richard S Blumberg

Nicole Beauchemin

Sara Najmeh

Jonathan Cools-Lartigue

Jonathan D Spicer

Lorenzo E Ferri

Affiliations

Soon will be listed here.

Abstract

Neutrophils promote tumor growth and metastasis at multiple stages of cancer progression. One mechanism through which this occurs is via release of neutrophil extracellular traps (NETs). We have previously shown that NETs trap tumor cells in both the liver and the lung, increasing their adhesion and metastasis following postoperative complications. Multiple studies have since shown that NETs play a role in tumor progression and metastasis. NETs are composed of nuclear DNA-derived web-like structures decorated with neutrophil-derived proteins. However, it is unknown which, if any, of these NET-affiliated proteins is responsible for inducing the metastatic phenotype. In this study, we identify the NET-associated carcinoembryonic Ag cell adhesion molecule 1 (CEACAM1) as an essential element for this interaction. Indeed, blocking CEACAM1 on NETs, or knocking it out in a murine model, leads to a significant decrease in colon carcinoma cell adhesion, migration and metastasis. Thus, this work identifies NET-associated CEACAM1 as a putative therapeutic target to prevent the metastatic progression of colon carcinoma.

Citing Articles

[Dual Roles of Neutrophil Extracellular Traps in Lung Cancer:  Mechanism Exploration and Therapeutic Prospects].

Li C, Peng D, Sun W Zhongguo Fei Ai Za Zhi. 2025; 28(1):63-68.

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The Role of Myeloid Cells on the Development of Hepatic Metastases in Gastrointestinal Cancer.

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PMID: 39790246 PMC: 11714404. DOI: 10.1016/j.gastha.2024.08.017.

The role of CEACAMs in neutrophil function.

Skubitz K Eur J Clin Invest. 2024; 54 Suppl 2:e14349.

PMID: 39674879 PMC: 11646290. DOI: 10.1111/eci.14349.

Mechanism and function of CEACAM1 splice isoforms.

Dery K, Najjar S, Beauchemin N, Shively J, Kupiec-Weglinski J Eur J Clin Invest. 2024; 54 Suppl 2:e14350.

PMID: 39674874 PMC: 11646291. DOI: 10.1111/eci.14350.

References

Gommerman J, Oh D, Zhou X, Tedder T, Maurer M, Galli S . A role for CD21/CD35 and CD19 in responses to acute septic peritonitis: a potential mechanism for mast cell activation. J Immunol. 2000; 165(12):6915-21. DOI: 10.4049/jimmunol.165.12.6915. View

Cools-Lartigue J, Spicer J, Najmeh S, Ferri L . Neutrophil extracellular traps in cancer progression. Cell Mol Life Sci. 2014; 71(21):4179-94. PMC: 7096049. DOI: 10.1007/s00018-014-1683-3. View

Cedervall J, Olsson A . Immunity Gone Astray - NETs in Cancer. Trends Cancer. 2017; 2(11):633-634. DOI: 10.1016/j.trecan.2016.10.012. View

Beauchemin N, Arabzadeh A . Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev. 2013; 32(3-4):643-71. DOI: 10.1007/s10555-013-9444-6. View

Skubitz K, Skubitz A . Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells. J Transl Med. 2008; 6:78. PMC: 2628881. DOI: 10.1186/1479-5876-6-78. View

Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss D . Neutrophil extracellular traps kill bacteria. Science. 2004; 303(5663):1532-5. DOI: 10.1126/science.1092385. View

Liu J, Di G, Wu C, Hu X, Duan H . Development and evaluation of a novel anti-colorectal cancer monoclonal antibody, WL5. Biochem Biophys Res Commun. 2013; 432(2):370-7. DOI: 10.1016/j.bbrc.2013.01.089. View

Najmeh S, Cools-Lartigue J, Rayes R, Gowing S, Vourtzoumis P, Bourdeau F . Neutrophil extracellular traps sequester circulating tumor cells via β1-integrin mediated interactions. Int J Cancer. 2017; 140(10):2321-2330. DOI: 10.1002/ijc.30635. View

Evans J, Sutton P, Winiarski B, Fenwick S, Malik H, Vimalachandran D . From mice to men: Murine models of colorectal cancer for use in translational research. Crit Rev Oncol Hematol. 2015; 98:94-105. DOI: 10.1016/j.critrevonc.2015.10.009. View

10.

Fridlender Z, Albelda S . Tumor-associated neutrophils: friend or foe?. Carcinogenesis. 2012; 33(5):949-55. DOI: 10.1093/carcin/bgs123. View

11.

Markel G, Ortenberg R, Seidman R, Sapoznik S, Koren-Morag N, Besser M . Systemic dysregulation of CEACAM1 in melanoma patients. Cancer Immunol Immunother. 2009; 59(2):215-30. PMC: 11030926. DOI: 10.1007/s00262-009-0740-5. View

12.

Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S, Giannias B . Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest. 2013; . PMC: 3726160. DOI: 10.1172/JCI67484. View

13.

Holmer R, Watzig G, Tiwari S, Rose-John S, Kalthoff H . Interleukin-6 trans-signaling increases the expression of carcinoembryonic antigen-related cell adhesion molecules 5 and 6 in colorectal cancer cells. BMC Cancer. 2015; 15:975. PMC: 4682226. DOI: 10.1186/s12885-015-1950-1. View

14.

Tilki D, Singer B, Shariat S, Behrend A, Fernando M, Irmak S . CEACAM1: a novel urinary marker for bladder cancer detection. Eur Urol. 2009; 57(4):648-54. DOI: 10.1016/j.eururo.2009.05.040. View

15.

Naci D, Vuori K, Aoudjit F . Alpha2beta1 integrin in cancer development and chemoresistance. Semin Cancer Biol. 2015; 35:145-53. DOI: 10.1016/j.semcancer.2015.08.004. View

16.

Ducker T, Skubitz K . Subcellular localization of CD66, CD67, and NCA in human neutrophils. J Leukoc Biol. 1992; 52(1):11-6. DOI: 10.1002/jlb.52.1.11. View

17.

Templeton A, McNamara M, Seruga B, Vera-Badillo F, Aneja P, Ocana A . Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014; 106(6):dju124. DOI: 10.1093/jnci/dju124. View

18.

Gu A, Zhang Z, Zhang N, Tsark W, Shively J . Generation of human CEACAM1 transgenic mice and binding of Neisseria Opa protein to their neutrophils. PLoS One. 2010; 5(4):e10067. PMC: 2852402. DOI: 10.1371/journal.pone.0010067. View

19.

Cuenca A, Delano M, Kelly-Scumpia K, Moldawer L, Efron P . Cecal ligation and puncture. Curr Protoc Immunol. 2010; Chapter 19:Unit 19.13. PMC: 3058382. DOI: 10.1002/0471142735.im1913s91. View

20.

Dankner M, Gray-Owen S, Huang Y, Blumberg R, Beauchemin N . CEACAM1 as a multi-purpose target for cancer immunotherapy. Oncoimmunology. 2017; 6(7):e1328336. PMC: 5543821. DOI: 10.1080/2162402X.2017.1328336. View