中国组织工程研究

中性粒细胞外诱捕网和活化血小板在肺癌研究中的进展与应用

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余代瑶 ¹,,² , 石平 ¹, , 杨兰 ¹,,² , 李知书 ¹, , 鲁永平 ¹,

中国组织工程研究 | 2026,30(1): 229-237

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中国组织工程研究 2026 , 30 (1) : 229 -237

中性粒细胞外诱捕网和活化血小板在肺癌研究中的进展与应用

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余代瑶¹,,², 石平¹,, 杨兰¹,,², 李知书¹,, 鲁永平¹,

作者信息

^1.元市中心医院，四川省广元市 628017

^2.北医学院，四川省南充市 637000

^3.元市中心医院，四川省广元市 628017

Advances and application of neutrophil extracellular traps and activated platelets in lung cancer research

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出版时间: 2026-01-08 doi: 10.12307/2025.580

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背景：中性粒细胞外诱捕网和活化血小板共同参与肺癌的侵袭、转移、生长及血管生成过程，与肺癌的发展、预后有着密切的关系。目的：综述中性粒细胞外诱捕网和活化血小板在肺癌中的作用机制以及在肺癌诊断、预后及治疗中的应用进展。方法：以“platelet activation，lung neoplasms，extracellular traps，treatment”为英文检索词，以“肺癌，中性粒细胞外诱捕网，血小板活化，P选择素，治疗”为中文检索词，检索PubMed和中国知网数据库。通过阅读文献标题和摘要进行初筛，再根据纳入标准及排除标准进行筛选、整理，最终纳入63篇相关性较高的文献。结果与结论：①肺癌诱导中性粒细胞外诱捕网的形成和血小板活化；②中性粒细胞外诱捕网和活化血小板共同促进肺癌的生长、转移；③中性粒细胞外诱捕网可作为肺癌诊断、疗效预测及进展监测的新型生物标志物；④靶向中性粒细胞外诱捕网、活化血小板可作为肺癌潜在的治疗手段。

关键词

肺癌 / 活化血小板 / 中性粒细胞外诱捕网 / 生物标志物 / 诊断

Abstract

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BACKGROUND: Neutrophil extracellular traps and activated platelets are involved in the invasion, metastasis, growth, and angiogenesis of lung cancer, and are closely related to the development and prognosis of lung cancer. OBJECTIVE: To review the mechanism of neutrophil extracellular traps and activated platelets in lung cancer and their application in diagnosis, prognosis, and treatment of lung cancer. METHODS: “Platelet activation, lung neoplasms, extracellular traps, treatment” for English search terms and “lung cancer, neutrophil-extracellular traps, platelet activation, P-selectin, treatment” for Chinese search terms were searched in PubMed and CNKI databases. After reading the title and abstract of the literature, according to the inclusion and exclusion criteria, 63 articles with high relevance were finally included. RESULTS AND CONCLUSION: (1) Formation of neutrophil extracellular traps and platelet activation were induced by lung tumor. (2) Neutrophil extracellular traps and activated platelets jointly promote the proliferation, growth and metastasis of lung cancer. (3) Neutrophil extracellular traps can be used as a novel biomarker for the diagnosis, prognosis and progression of lung cancer. (4) Targeting neutrophil extracellular traps and activating platelets can be used as potential therapies for lung cancer.

Key words

lung cancer / activated platelet / neutrophil extracellular trap / biomarker / diagnosis

引用本文

余代瑶, 石平, 杨兰, 李知书, 鲁永平. 中性粒细胞外诱捕网和活化血小板在肺癌研究中的进展与应用. 中国组织工程研究, 2026 , 30 (1) : 229 -237 . DOI: 10.12307/2025.580

. Advances and application of neutrophil extracellular traps and activated platelets in lung cancer research[J]. Chinese Journal of Tissue Engineering Research, 2026 , 30 (1) : 229 -237 . DOI: 10.12307/2025.580

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四川省自然科学基金面上项目

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ZHAO F, LI L, GUAN L, et al. Roles for GP IIb/IIIa and αvβ3 integrins in MDA-MB-231 cell invasion and shear flow-induced cancer cell mechanotransduction. Cancer Lett. 2014; 344(1):62-73.

QI CL, WEI B, YE J, et al. P-selectin-mediated platelet adhesion promotes the metastasis of murine melanoma cells. PLoS One. 2014; 9(3):e91320.

ZHENG RS, CHEN R, HAN BF, et al. Cancer incidence and mortality in China, 2022. Zhonghua Zhong Liu Za Zhi. 2024;46(3):221-231.

MILLER KD, SIEGEL RL, LIN CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66(4):271-289.

GORUDKO IV, SOKOLOV AV, SHAMOVA EV, et al. Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry. Biol Open. 2013;2(9):916-923.

ZHOU J, YANG Y, GAN T, et al. Lung cancer cells release high mobility group box 1 and promote the formation of neutrophil extracellular traps. Oncol Lett. 2019;18(1):181-188.

ANSARI D, ANSARI D, ANDERSSON R, et al. Pancreatic cancer and thromboembolic disease, 150 years after Trousseau. Hepatobiliary Surg Nutr. 2015;4(5):325-335.

BRAUN A, ANDERS HJ, GUDERMANN T, et al. Platelet-Cancer Interplay: Molecular Mechanisms and New Therapeutic Avenues. Front Oncol. 2021;11:665534.

HUANG J, LI X, SHI X, et al. Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting. J Hematol Oncol. 2019;12(1):26.

YANG L, LIU Q, ZHANG X, et al. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature. 2020; 583(7814):133-138.

GONG L, MI HJ, ZHU H, et al. P-selectin-mediated platelet activation promotes adhesion of non-small cell lung carcinoma cells on vascular endothelial cells under flow. Mol Med Rep. 2012;5(4):935-942.

BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263.

LI X, HU L, NAEEM A, et al. Neutrophil Extracellular Traps in Tumors and Potential Use of Traditional Herbal Medicine Formulations for Its Regulation. Int J Nanomedicine. 2024; 19:2851-2877.

REN J, HE J, ZHANG H, et al. Platelet TLR4-ERK5 Axis Facilitates NET-Mediated Capturing of Circulating Tumor Cells and Distant Metastasis after Surgical Stress. Cancer Res. 2021;81(9): 2373-2385.

FANG C, LIU F, WANG Y, et al. A innovative prognostic symbol based on neutrophil extracellular traps (NETs)-related lncRNA signature in non-small-cell lung cancer. Aging (Albany NY). 2021;13(13):17864-17879.

FANG R, ZHU Y, KHADKA VS, et al. The Evaluation of Serum Biomarkers for Non-small Cell Lung Cancer (NSCLC) Diagnosis. Front Physiol. 2018;9:1710.

FUCHS TA, BRILL A, DUERSCHMIED D, et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A. 2010; 107(36):15880-15885.

DEMERS M, WONG SL, MARTINOD K, et al. Priming of neutrophils toward NETosis promotes tumor growth. Oncoimmunology. 2016;5(5):e1134073.

任鹏飞,王弦,李晶晶,等.非小细胞肺癌中PDGF-BB表达及其与骨转移的相关性[J].临床与实验病理杂志,2021,37(6):669-673.

BERGER-ACHITUV S, BRINKMANN V, ABED UA, et al. A proposed role for neutrophil extracellular traps in cancer immunoediting. Front Immunol. 2013;4:48.

FUCHS TA, ABED U, GOOSMANN C, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176(2):231-241.

ALBRENGUES J, SHIELDS MA, NG D, et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science. 2018;361(6409):eaao4227.

ZUO Y, LENG G, LENG P. Identification and validation of molecular subtype and prognostic signature for lung adenocarcinoma based on neutrophil extracellular traps. Pathol Oncol Res. 2023;29:1610899.

WIRTZ D, KONSTANTOPOULOS K, SEARSON PC. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer. 2011;11(7):512-522.

SUZUKI-INOUE K. Platelets and cancer-associated thrombosis: focusing on the platelet activation receptor CLEC-2 and podoplanin. Blood. 2019;134(22):1912-1918.

ROTHWELL PM, PRICE JF, FOWKES FG, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379(9826):1602-1612.

XIA Q, ZHANG X, CHEN Q, et al. Down-regulation of tissue factor inhibits invasion and metastasis of non-small cell lung cancer. J Cancer. 2020;11(5):1195-1202.

DEMERS M, KRAUSE DS, SCHATZBERG D, et al. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci U S A. 2012;109(32):13076-13081.

BRINKMANN V, REICHARD U, GOOSMANN C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532-1535.

YAZDANI HO, ROY E, COMERCI AJ, et al. Neutrophil Extracellular Traps Drive Mitochondrial Homeostasis in Tumors to Augment Growth. Cancer Res. 2019;79(21): 5626-5639.

MIYATA K, TAKEMOTO A, OKUMURA S, et al. Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation. Sci Rep. 2017;7(1):4059.

HO-TIN-NOÉ B, GOERGE T, CIFUNI SM, et al. Platelet granule secretion continuously prevents intratumor hemorrhage. Cancer Res. 2008;68(16):6851-6858.

WIGERBLAD G, KAPLAN MJ. Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases. Nat Rev Immunol. 2023;23(5):274-288.

CHEN D, LIANG H, HUANG L, et al. Liraglutide enhances the effect of checkpoint blockade in lung and liver cancers through the inhibition of neutrophil extracellular traps. FEBS Open Bio. 2024;14(8):1365-1377.

RASKOV H, ORHAN A, AGERBÆK MØ, et al. The impact of platelets on the metastatic potential of tumour cells. Heliyon. 2024; 10(14):e34361.

OKLU R, SHETH RA, WONG KHK, et al. Neutrophil extracellular traps are increased in cancer patients but does not associate with venous thrombosis. Cardiovasc Diagn Ther. 2017;7(Suppl 3):S140-S149.

MASSBERG S, GRAHL L, VON BRUEHL ML, et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. 2010;16(8):887-896.

LI M, LIN C, DENG H, et al. A Novel Peptidylarginine Deiminase 4 (PAD4) Inhibitor BMS-P5 Blocks Formation of Neutrophil Extracellular Traps and Delays Progression of Multiple Myeloma. Mol Cancer Ther. 2020; 19(7):1530-1538.

LI B, ZHU T, WU X, et al. The crosstalk between lung cancer cells and platelets promotes tumor angiogenesis in vivo and in vitro. J Cancer Res Clin Oncol. 2023;149(7):3495-3511.

RAYES RF, MOUHANNA JG, NICOLAU I, et al. Primary tumors induce neutrophil extracellular traps with targetable metastasis promoting effects. JCI Insight. 2019;5(16):e128008.

TONG H, LI K, ZHOU M, et al. Coculture of cancer cells with platelets increases their survival and metastasis by activating the TGFβ/Smad/PAI-1 and PI3K/AKT pathways. Int J Biol Sci. 2023;19(13):4259-4277.

LIU Y, ZHANG Y, DING Y, et al. Platelet-mediated tumor metastasis mechanism and the role of cell adhesion molecules. Crit Rev Oncol Hematol. 2021;167:103502.

HU M, HU Y, HE J, et al. Prognostic Value of Basic Fibroblast Growth Factor (bFGF) in Lung Cancer: A Systematic Review with Meta-Analysis. PLoS One. 2016;11(1):e0147374.

WANG Y, LIU F, CHEN L, et al. Neutrophil Extracellular Traps (NETs) Promote Non-Small Cell Lung Cancer Metastasis by Suppressing lncRNA MIR503HG to Activate the NF-κB/NLRP3 Inflammasome Pathway. Front Immunol. 2022;13:867516.

TARRANT BJ, SNELL G, IVULICH S, et al. Dornase alfa during lower respiratory tract infection post-lung transplantation: a randomized controlled trial. Transpl Int. 2019;32(6):603-613.

ABDOL RAZAK N, ELASKALANI O, METHAROM P. Pancreatic Cancer-Induced Neutrophil Extracellular Traps: A Potential Contributor to Cancer-Associated Thrombosis. Int J Mol Sci. 2017;18(3):487.

LABELLE M, HYNES RO. The initial hours of metastasis: the importance of cooperative host-tumor cell interactions during hematogenous dissemination. Cancer Discov. 2012;2(12):1091-1099.

KALTENMEIER C, YAZDANI HO, MORDER K, et al. Neutrophil Extracellular Traps Promote T Cell Exhaustion in the Tumor Microenvironment. Front Immunol. 2021;12: 785222.

ZENG X, LI J, PEI L, et al. Didang decoction attenuates cancer-associated thrombosis by inhibiting PAD4-dependent NET formation in lung cancer. Pulm Circ. 2024;14(4):e12454.

JUNG HS, GU J, KIM JE, et al. Cancer cell-induced neutrophil extracellular traps promote both hypercoagulability and cancer progression. PLoS One. 2019;14(4): e0216055.

WANG M, LV X, WANG Y, et al. Biomarkers of peripheral blood neutrophil extracellular traps in the diagnosis and progression of malignant tumors. Cancer Med. 2024;13(3):e6935.

ZHOU L, ZHANG Z, TIAN Y, et al. The critical role of platelet in cancer progression and metastasis. Eur J Med Res. 2023;28(1):385.

ZHOU X, WU C, WANG X, et al. Tumor cell-released autophagosomes (TRAPs) induce PD-L1-decorated NETs that suppress T-cell function to promote breast cancer pulmonary metastasis. J Immunother Cancer. 2024;12(6):e009082.

ETULAIN J, MARTINOD K, WONG SL, et al. P-selectin promotes neutrophil extracellular trap formation in mice. Blood. 2015;126(2):242-246.

COOLS-LARTIGUE J, SPICER J, MCDONALD B, et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest. 2013; 123(8):3446-3458.

NAJMEH S, COOLS-LARTIGUE J, RAYES RF, et al. Neutrophil extracellular traps sequester circulating tumor cells via β1-integrin mediated interactions. Int J Cancer. 2017;140(10):2321-2330.

LABELLE M, BEGUM S, HYNES RO. Platelets guide the formation of early metastatic niches. Proc Natl Acad Sci U S A. 2014;111(30):E3053-3061.

XIAO Y, CONG M, LI J, et al. Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation. Cancer Cell. 2021;39(3):423-437.e7.

TEIJEIRA Á, GARASA S, GATO M, et al. CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity. Immunity. 2020;52(5):856-871.e8.

HOUGHTON AM, RZYMKIEWICZ DM, JI H, et al. Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth. Nat Med. 2010;16(2):219-223.

PENG YP, ZHANG JJ, LIANG WB, et al. Elevation of MMP-9 and IDO induced by pancreatic cancer cells mediates natural killer cell dysfunction. BMC Cancer. 2014;14:738.

LI Y, YANG Y, GAN T, et al. Extracellular RNAs from lung cancer cells activate epithelial cells and induce neutrophil extracellular traps. Int J Oncol. 2019;55(1):69-80.

HALLY KE, PARKER OM, BRUNTON-O’SULLIVAN MM, et al. Linking Neutrophil Extracellular Traps and Platelet Activation: A Composite Biomarker Score for Predicting Outcomes after Acute Myocardial Infarction. Thromb Haemost. 2021;121(12):1637-1649.

2026年第30卷第1期

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doi: 10.12307/2025.580

首发时间：2025-05-30
出版时间：2026-01-08

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录用日期：2025-03-27

基金

四川省自然科学基金面上项目

作者信息

^1.元市中心医院，四川省广元市 628017

^2.北医学院，四川省南充市 637000

^3.元市中心医院，四川省广元市 628017

通讯作者:

石平: 石平，硕士，硕士生导师，主任医师，广元市中心医院，四川省广元市 628017

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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