外泌体在胃癌中的研究进展
Research Progress of Exosome in Gastric Cancer
DOI: 10.12677/ACM.2022.12101338, PDF,   
作者: 陈 鑫, 李林俞：甘肃中医药大学第一临床医学院，甘肃 兰州；甘肃省人民医院肿瘤内科，甘肃 兰州；郑金平：宁夏石嘴山市第二人民医院神经外科，宁夏 石嘴山；李红玲*：甘肃省人民医院肿瘤内科，甘肃 兰州
关键词: 胃癌；外泌体；肿瘤微环境；MEK-ERK信号通路；Gastric Cancer； Exosome； TME； MEK-ERK Signaling Pathway
摘要: 外泌体是直径在30~150 nm的脂质双分子层的小囊泡，携带多种细胞相关特异性活性物质。在胃癌微环境中胃癌细胞分泌的外泌体参与肿瘤的生长，细胞增殖，细胞侵袭转移及血管生成等过程。已有研究表明胃癌细胞外泌体与巨噬细胞增殖、迁移密切相关。但缺氧条件下胃癌细胞外泌体诱导巨噬细胞极化的具体途径和机制尚不明确。本文就胃癌细胞外泌体内容物介导MEK-ERK信号通路对巨噬细胞极化表型的影响及研究进展进行综述，旨在探讨外泌体在胃癌治疗中的潜在价值，为胃癌的治疗提供新的靶点。
Abstract: Exosomes are small vesicles of lipid bilayers with diameters ranging from 30 nm~150 nm, which carry a variety of cell-related specific active substances. Exosomes secreted by gastric cancer cells in the microenvironment of gastric cancer are involved in tumor growth, cell proliferation, cell inva-sion, metastasis, and angiogenesis. Previous studies have shown that gastric cancer exosomes are closely related to macrophage proliferation and migration. However, the specific pathway and mechanism of macrophage polarization induced by exosome in gastric cancer cells under hypoxia are still unclear. This article reviews the effect and research progress of MEK-ERK signaling path-way mediated by exosome contents of gastric cancer cells on the polarization phenotype of macro-phages, aiming to explore the potential value of exosome in the treatment of gastric cancer and provide new targets for the treatment of gastric cancer.
文章引用：陈鑫, 郑金平, 李林俞, 李红玲. 外泌体在胃癌中的研究进展[J]. 临床医学进展, 2022, 12(10): 9255-9260. https://doi.org/10.12677/ACM.2022.12101338

参考文献

[1] Wang, F.H., Zhang, X.T., Li, Y.F., et al. (2021) The Chinese Society of Clinical Oncology (CSCO): Clinical Guidelines for the Diagnosis and Treatment of Gastric Cancer, 2021. Cancer Communications (London), 41, 747-795. [Google Scholar] [CrossRef] [PubMed]
[2] Song, Z., Wu, Y., Yang, J., Yang, D. and Fang, X. (2017) Progress in the Treatment of Advanced Gastric Cancer. Tumor Biology, 39. [Google Scholar] [CrossRef] [PubMed]
[3] 艾晓青, 窦磊. 外泌体优化策略的研究进展[J]. 临床医学研究与践, 2021, 6(16): 190-192.
[4] Tiwari, S., Kumar, V., Randhawa, S., et al. (2021) Preparation and Characterization of Extracellular Vesicles. American Journal of Reproductive Immunology, 85, e13367. [Google Scholar] [CrossRef] [PubMed]
[5] Ruffell, B. and Coussens, L.M. (2015) Macro-phages and Therapeutic Resistance in Cancer. Cancer Cell, 27, 462-472. [Google Scholar] [CrossRef] [PubMed]
[6] Cardoso, A.P., Pinto, M.L., Pinto, A.T., et al. (2014) Macrophages Stimulate Gastric and Colorectal Cancer Invasion through EGFR Y (1086), c-Src, Erk1/2 and Akt Phosphorylation and Small GTPase Activity. Oncogene, 33, 2123-2133. [Google Scholar] [CrossRef] [PubMed]
[7] Chen, W., Zheng, R., Baade, P.D., Zhang, S., Zeng, H., Bray, F., Jemal, A., Yu, X.Q. and He, J. (2016) Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 66, 115-132. [Google Scholar] [CrossRef] [PubMed]
[8] Yusefi, A.R., Bagheri Lan-karani, K., Bastani, P., Radinmanesh, M. and Kavosi, Z. (2018) Risk Factors for Gastric Cancer: A Systematic Review. Asian Pacific Journal of Cancer Prevention, 19, 591-603.
[9] Chung, C.S., Lee, Y.C. and Wu, M.S. (2015) Prevention Strategies for Esophageal Cancer: Perspectives of the East vs. West. Best Practice & Research. Clinical Gastroenterology, 29, 869-883. [Google Scholar] [CrossRef] [PubMed]
[10] Tsai, M.M., Wang, C.S., Tsai, C.Y., Huang, H.W., Chi, H.C., Lin, Y.H., Lu, P.H. and Lin, K.H. (2016) Potential Diagnostic, Prognostic and Therapeutic Targets of Mi-croRNAs in Human Gastric Cancer. International Journal of Molecular Sciences, 17, Article No. 945. [Google Scholar] [CrossRef] [PubMed]
[11] Emoto, S., Ishigami, H., Yamashita, H., Yamaguchi, H., Kaisaki, S. and Kitayama, J. (2012) Clinical Significance of CA125 and CA72-4 in Gastric Cancer with Peritoneal Dissemination. Gas-tric Cancer, 15, 154-161. [Google Scholar] [CrossRef] [PubMed]
[12] 陈德义, 苏刚, 刘骥飞, 吴琼慧, 陈玮, 张振昶. 外泌体载体治疗在中枢神经系统疾病中的研究进展[J]. 中国细胞生物学学报, 2021, 43(8): 1650-1657.
[13] Zhou, Y.Y., et al. (2017) Exosome Transfer among Different Species Cells and Mediating miRNAs Delivery. Journal of Cellular Bio-chemistry, 118, 4267-4274. [Google Scholar] [CrossRef] [PubMed]
[14] Zhang, Y., Bi, J., Huang, J., Tang, Y., Du, S. and Li, P. (2020) Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications. International Journal of Nanomedicine, 15, 6917-6934. [Google Scholar] [CrossRef] 
[15] Cheng, L., Zhang, K., Wu, S.Y., Cui, M.H. and Xu, T.M. (2017) Focus on Mesenchymal Stem Cell-Derived Exosome: Opportunities and Challenges in Cell-Free Therapy. Stem Cells Interna-tional, 2017, Article ID: 6305295. [Google Scholar] [CrossRef] [PubMed]
[16] He, C.Q., Hua, W., Liu, J.T., Fan, L.L., Wang, H. and Sun, G.P. (2020) Exosome Derived from Endoplasmic Reticulum-Stressed Liver Cancer Cells Enhance the Expression of Cytokines in Macrophages via the STAT3 Signaling Pathway. Oncology Letters, 20, 589-600. [Google Scholar] [CrossRef] [PubMed]
[17] Li, D.P., Wang, Y., Jin, X.R., et al. (2020) NK Cell-Derived Exosome Carry miR-207 and Alleviate Depression-Like Symptoms in Mice. Journal of Neuroinflammation, 17, Article No. 126. [Google Scholar] [CrossRef] [PubMed]
[18] Zhao, D.Y., Yu, Z.C., Li, Y., Wang, Y., Li, Q.F. and Han, D. (2020) GelMA Combined with Sustained Release of HUVECs Derived Exosome for Promoting Cutaneous Wound Healing and Facilitating Skin Regeneration. Journal of Molecular Histology, 51, 251-263. [Google Scholar] [CrossRef] [PubMed]
[19] Thery, C., Witwer, K., Aikawa, E., et al. (2018) Minimal Infor-mation for Studies of Extracellular Vesicles 2018 (MISEV2018): A Position Statement of the International Society for Extracellular Vesicles and Update of the MISEV2014 Guidelines. Journal of Extracellular Vesicles, 7, Article ID: 1535750. [Google Scholar] [CrossRef] [PubMed]
[20] 黄哲. 缺氧大肠癌细胞来源的外泌体通过Wnt4介导的β-catenin信号通路促进肿瘤血管新生及转移的机制研究[D]: [博士学位论文]. 沈阳: 中国医科大学, 2019.
[21] 苏刚. 分泌蛋白及外泌体对肝癌细胞影响的蛋白质组学研究[D]: [博士学位论文]. 兰州: 兰州大学, 2018.
[22] Abdelnaby, K., et al. (2016) Circulating Exosome Potentiate Tumor Malignant Properties in a Mouse Model of Chronic Sleep Fragmentation. Oncotarget, 7, 54676-54690. [Google Scholar] [CrossRef] [PubMed]
[23] 张佳佳, 苏刚, 陈丽霞, 王满侠, 周娟平, 高娟, 张振昶. 缺氧条件下中枢神经系统外泌体作用机制[J]. 中国细胞生物学学报, 2021, 43(1): 103-109.
[24] 王琳琳, 朱桂全, 李灵. 缺氧肿瘤微环境中外泌体参与免疫调控的研究进展[J]. 细胞与分子免疫学杂志, 2021, 37(7): 651-656.
[25] Walbrecq, G., et al. (2020) Distinct Cargos of Small Extracellular Vesicles Derived from Hypoxic Cells and Their Effect on Cancer Cells. International Journal of Molecular Sciences, 21, Article No. 5071. [Google Scholar] [CrossRef] [PubMed]
[26] Kuo, T.C., Kung, H.J. and Shih, J.W. (2020) Signaling in and out: Long-Noncoding RNAs in Tumor Hypoxia. Journal of Biomedical Science, 27, Article No. 59. [Google Scholar] [CrossRef] [PubMed]
[27] Doyle, L.M. and Wang, M.Z. (2019) Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 8, Article No. 727. [Google Scholar] [CrossRef] [PubMed]
[28] Taheri, B., Soleimani, M., Aval, S.F., Memari, F. and Zarghami, N. (2018) C6 Glioma-Derived Microvesicles Stimulate the Proliferative and Metastatic Gene Expression of Normal Astro-cytes. Neuroscience Letters, 685, 173-178. [Google Scholar] [CrossRef] [PubMed]
[29] Laviron, M. and Boissonnas, A. (2019) Ontogeny of Tu-mor-Associated Macrophages. Frontiers in Immunology, 10, Article No. 1799. [Google Scholar] [CrossRef] [PubMed]
[30] Isidro, R.A. and Appleyard, C.B. (2016) Colonic Macrophage Po-larization in Homeostasis, Inflammation, and Cancer. The American Journal of Physiology-Gastrointestinal and Liver Physiology, 311, G59-G73. [Google Scholar] [CrossRef] [PubMed]
[31] 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(5): 679-685.
[32] Singh, S., Mehta, N., Jiang, L.L., et al. (2017) Initiative Action of Tumor Associated Macrophage during Tumor Metastasis. Biochimie Open, 4, 8-18. [Google Scholar] [CrossRef] [PubMed]
[33] 王一晨, 杨文山, 董宪喆, 胡园. 肿瘤相关巨噬细胞的作用综述[J]. 解放军医学院学报, 2021, 42(12): 1315-1321.
[34] Vitale, I., Manic, G., Coussens, L.M., Kroemer, G. and Galluzzi, L. (2019) Macrophages and Metabolism in the Tumor Microenvironment. Cell Metabolism, 30, 36-50. [Google Scholar] [CrossRef] [PubMed]
[35] Oya, Y., Hayakawa, Y. and Koike, K. (2020) Tumor Microenvi-ronment in Gastric Cancers. Cancer Science, 111, 2696-2707. [Google Scholar] [CrossRef] [PubMed]
[36] Netea-Maier, R.T., Smit, J.W.A. and Netea, M.G. (2018) Metabolic Changes in Tumor Cells and Tumor-Associated Macrophages: A Mutual Relationship. Cancer Letters, 413, 102-109. [Google Scholar] [CrossRef] [PubMed]
[37] Lewis, C.E. and Pollard, J.W. (2006) Distinct Role of Macrophages in Different Tumor Microenvironments. Cancer Research, 66, 605-612. [Google Scholar] [CrossRef] 
[38] 李丽伟. 胃癌中PTEN低表达通过上调P-AURKA调节AURKA是维持胃癌恶性表型的本质[D]: [硕士学位论文]. 天津: 天津医科大学, 2018.
[39] Wang, D., Boerner, S.A., Winkler, J.D., et al. (2007) Clinical Experience of MEK Inhibitors in Cancer Therapy. Biochimicaet Biophysica Acta, 1773, 1248-1255. [Google Scholar] [CrossRef] [PubMed]
[40] Martin-Liberal, J., Lagares-Tena, L. and Larkin, J. (2014) Pro-spects for MEK Inhibitors for Treating Cancer. Expert Opinion Drug Safety, 13, 483-495. [Google Scholar] [CrossRef] [PubMed]
[41] Chen, H., Jin, Z.L. and Xu, H. (2016) MEK/ERK Signaling Pathway in Apoptosis of SW620 Cell Line and Inhibition Effect of Resveratrol. Asian Pacific Journal of Tropical Medi-cine, 9, 49-53. [Google Scholar] [CrossRef] [PubMed]
[42] Li, B., Lv, L. and Li, W. (2020) 1,25-Dihydroxy Vitamin D3 In-hibits the Ras-MEK-ERK Pathway and Regulates Proliferation and Apoptosis of Papillary Thyroid Carcinoma. Steroids, 159, Article ID: 108585. [Google Scholar] [CrossRef] [PubMed]
[43] Zhao, J., Klausen, C., Yi, Y., et al. (2020) Betacellulin En-hances Ovarian Cancer Cell Migration by Up-Regulating Connexin43 via MEK-ERK Signaling. Cell Signal, 65, Article ID: 109439. [Google Scholar] [CrossRef] [PubMed]
[44] Ma, R., Wang, L., Yuan, F., et al. (2018) FABP7 Promotes Cell Proliferation and Survival in Colon Cancer through MEK/ERK Signaling Pathway. Biomedicine & Pharmacotherapy, 108, 119-129. [Google Scholar] [CrossRef] [PubMed]
[45] Buscà, R., Christen, R., Lovern, M., et al. (2015) ERK1 and ERK2 Present Functional Redundancy in Tetrapods Despite Higher Evolution Rate of ERK1. BMC Evolutionary Biology, 15, Article No. 179. [Google Scholar] [CrossRef] [PubMed]
[46] Reddy, K.B., Nabha, S.M. and Atanaskova, N. (2003) Role of MAP Kinase in Tumor Progression and Invasion. Cancer and Metastasis Reviews, 22, 395-403. [Google Scholar] [CrossRef] 
[47] Sun, Y., Liu, W.Z., Liu, T., et al. (2015) Signaling Pathway of MAPK/ERK in Cell Proliferation, Differentiation, Migration, Senescence and Apoptosis. Journal of Receptor and Signal Transduction Research, 35, 600-604. [Google Scholar] [CrossRef] [PubMed]
[48] Calvo, N., Martín, M.J., De Boland, A.R., et al. (2014) In-volvement of ERK1/2, p38 MAPK, and PI3K/Akt Signaling Pathways in the Regulation of Cell Cycle Progression by PTHrP in Colon Adenocarcinoma Cells. Biochemistry and Cell Biology, 92, 305-315. [Google Scholar] [CrossRef] [PubMed]
[49] Chambard, J.C., Lefloch, R., Pouysségur, J. and Lenormand, P. (2007) ERK Implication in Cell Cycle Regulation. Biochimica et Biophysica Acta, 1773, 1299-1310. [Google Scholar] [CrossRef] [PubMed]
[50] 陆紫媛, 肖扬, 李力, 王耀春. TNF-α通过ERK信号通路刺激骨髓间充质干细胞表达VCAM-1 [J]. 中国实验血液学杂志, 2013, 21(6): 1568-1571.

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