Exosome as a crucial communicator between tumor microenvironment and gastric cancer (Review)

Wang,Menghui; Shu,Hongxin; Cheng,Xifu; Xiao,Hong; Jin,Zhenhua; Yao,Nan; Mao,Shengxun; Zong,Zhen

doi:10.3892/ijo.2024.5616

Exosome as a crucial communicator between tumor microenvironment and gastric cancer (Review)

Authors:
- Menghui Wang
- Hongxin Shu
- Xifu Cheng
- Hong Xiao
- Zhenhua Jin
- Nan Yao
- Shengxun Mao
- Zhen Zong
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Affiliations: Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, School of Ophthalmology and Optometry, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Queen Marry College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: January 19, 2024 https://doi.org/10.3892/ijo.2024.5616
Article Number: 28
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer is one of the most common malignancies and has relatively high morbidity and mortality rates. Exosomes are nanoscale extracellular vesicles that originate from a diverse array of cells and may be found throughout various bodily fluids. These vesicles are endogenous nanocarriers in their natural state with the unique ability to transport lipids, proteins, DNA and RNA. Exosomes contain DNA, RNA, proteins, lipids and other bioactive components that have crucial roles in the transmission of information and regulation of cell activities in gastric cancer. This paper begins with an exploration of the composition, formation and release mechanisms of exosomes. Subsequently, the role of exosomes in the tumor microenvironment is reviewed in terms of the immune cell population, nonimmune cell population and other factors. Finally, the current status and challenges of exosome‑based research on the progression, diagnosis and therapeutic methods of gastric cancer are summarized. This holistic review offers insight that may guide future research directions for exosomes and potentially pave the way for novel therapeutic interventions in the management of gastric cancer.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011.
2	Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer Statistics, 2021. CA Cancer J Clin. 71:7–33. 2021.
3	Estevez-Ordonez D, Montalvan-Sanchez EE, Wong RE, Montalvan-Sanchez DM, Rodriguez-Murillo AA, Dominguez RL and Morgan DR: Health barriers and patterns of gastric cancer care in rural central American resource-limited settings. JAMA Oncol. 4:1131–1133. 2018.
4	Yeoh KG and Tan P: Mapping the genomic diaspora of gastric cancer. Nat Rev Cancer. 22:71–84. 2022.
5	Walker MM, Teare L and McNulty C: Gastric cancer and Helicobacter pylori: The bug, the host or the environment? Postgrad Med J. 84:169–170. 2008.
6	Zeyaullah M, AlShahrani AM and Ahmad I: Association of helicobacter pylori infection and host cytokine gene polymorphism with gastric cancer. Can J Gastroenterol Hepatol. 2021:88106202021.
7	Zeng Y and Jin RU: Molecular pathogenesis, targeted therapies, and future perspectives for gastric cancer. Semin Cancer Biol. 86:566–582. 2021.
8	Trams EG, Lauter CJ, Salem N and Heine U: Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta. 645:63–70. 1981.
9	Li Y, Tian L, Zhao T and Zhang J: A nanotherapeutic system for gastric cancer suppression by synergistic chemotherapy and immunotherapy based on iPSCs and DCs exosomes. Cancer Immunol Immunother. 72:1673–1683. 2023.
10	Chen BY, Sung CWH, Chen C, Cheng CM, Lin DP, Huang CT and Hsu MY: Advances in exosomes technology. Clin Chim Acta. 493:14–19. 2019.
11	Beit-Yannai E, Tabak S and Stamer WD: Exosomes. Nat Biotechnol. 38:11502020.
12	Ayyar KK and Moss AC: Exosomes in intestinal inflammation. Front Pharmacol. 12:6585052021.
13	Beit-Yannai E, Tabak S and Stamer WD: Physical exosome: Exosome interactions. J Cell Mol Med. 22:2001–2006. 2018.
14	Wang J, Liu Y, Sun W, Zhang Q, Gu T and Li G: Plasma exosomes as novel biomarker for the early diagnosis of gastric cancer. Cancer Biomark. 21:805–812. 2018.
15	Xia Y, Hu X, Di K, Liu C, Tan T, Lin Y, Xu H, Xie H, Wang S, Yang Z, et al: Combined detection of exosome concentration and tumor markers in gastric cancer. J Biomed Nanotechnol. 16:252–258. 2020.
16	Exosomes. Nat Biotechnol. 38:11502020.
17	Li J, Zhang Y and Luo B: Effects of exosomal viral components on the tumor microenvironment. Cancers (Basel). 14:35522022.
18	Pegtel DM and Gould SJ: Exosomes. Annu Rev Biochem. 88:487–514. 2019.
19	Wang X, Huang J, Chen W, Li G, Li Z and Lei J: The updated role of exosomal proteins in the diagnosis, prognosis, and treatment of cancer. Exp Mol Med. 54:1390–1400. 2022.
20	Wang M, Zhao X, Huang F, Wang L, Huang J, Gong Z and Yu W: Exosomal proteins: Key players mediating pre-metastatic niche formation and clinical implications (Review). Int J Oncol. 58:42021.
21	Huda MN and Nurunnabi M: Potential application of exosomes in vaccine development and delivery. Pharm Res. 39:2635–2671. 2022.
22	Wang W, Zhu N, Yan T, Shi YN, Chen J, Zhang CJ, Xie XJ, Liao DF and Qin L: The crosstalk: Exosomes and lipid metabolism. Cell Commun Signal. 18:1192020.
23	Puno MR, Weick E-M, Das M and Lima CD: SnapShot: The RNA exosome. Cell. 179:282–282.e1. 2019.
24	Kilchert C, Wittmann S and Vasiljeva L: The regulation and functions of the nuclear RNA exosome complex. Nat Rev Mol Cell Biol. 17:227–239. 2016.
25	Bach DH, Hong JY, Park HJ and Lee SK: The role of exosomes and miRNAs in drug-resistance of cancer cells. Int J Cancer. 141:220–230. 2017.
26	Wu Z, Fang ZX, Hou YY, Wu BX, Deng Y, Wu HT and Liu J: Exosomes in metastasis of colorectal cancers: Friends or foes? World J Gastrointest Oncol. 15:731–756. 2023.
27	Patil AA and Rhee WJ: Exosomes: Biogenesis, composition, functions, and their role in pre-metastatic niche formation. Biotechnol Bioprocess Engineering. 24:689–701. 2019.
28	Kanemoto S, Nitani R, Murakami T, Kaneko M, Asada R, Matsuhisa K, Saito A and Imaizumi K: Multivesicular body formation enhancement and exosome release during endoplasmic reticulum stress. Biochem Biophys Res Commun. 480:166–172. 2016.
29	Xia Z, Qing B, Wang W, Gu L, Chen H and Yuan Y: Formation, contents, functions of exosomes and their potential in lung cancer diagnostics and therapeutics. Thorac Cancer. 12:3088–3100. 2021.
30	Wang Z, Zhao Z, Gao B and Zhang L: Exosome mediated biological functions within skeletal microenvironment. Front Bioeng Biotechnol. 10:9539162022.
31	Zhang Y, Liu Y, Liu H and Tang WH: Exosomes: Biogenesis, biologic function and clinical potential. Cell Biosci. 9:192019.
32	Kuang G, Wang Z, Luo C, Luo J and Wang J: Mechanism of exosomes in the tumor microenvironment in the abscopal effect (Review). Int J Oncol. 62:22023.
33	Han L, Lam EWF and Sun Y: Extracellular vesicles in the tumor microenvironment: Old stories, but new tales. Mol Cancer. 18:592019.
34	Anderson NM and Simon MC: The tumor microenvironment. Curr Biol. 30:R921–R925. 2020.
35	Guerra E, Di Pietro R, Basile M, Trerotola M and Alberti S: Cancer-Homing CAR-T cells and endogenous immune population dynamics. Int J Mol Sci. 23:4052021.
36	Kong H and Kim SB: Exosomal communication between the tumor microenvironment and innate immunity and its therapeutic application. Immune Netw. 22:e382022.
37	Wang Z, Chen JQ, Liu JL and Tian L: Exosomes in tumor microenvironment: Novel transporters and biomarkers. J Transl Med. 14:2972016.
38	Louise F, Ken YL, Richard BSR, Chien-Fu H and Wu TC: Cervical cancer immunotherapy: Facts and hopes. Clin Cancer Res. 27:4953–4973. 2021.
39	Li I and Nabet BY: Exosomes in the tumor microenvironment as mediators of cancer therapy resistance. Mol Cancer. 18:322019.
40	Hu X, Qiu Y, Zeng X and Wang H: Exosomes reveal the dual nature of radiotherapy in tumor immunology. Cancer Sci. 113:1105–1112. 2022.
41	Baig MS, Roy A, Rajpoot S, Liu D, Savai R, Banerjee S, Kawada M, Faisal SM, Saluja R, Saqib U, et al: Tumor-derived exosomes in the regulation of macrophage polarization. Inflamm Res. 69:435–451. 2020.
42	Yunna C, Mengru H, Lei W and Weidong C: Macrophage M1/M2 polarization. Eur J Pharmacol. 877:1730902020.
43	Xia Y, Rao L, Yao H, Wang Z, Ning P and Chen X: Engineering macrophages for cancer immunotherapy and drug delivery. Adv Mater. 32:e20020542020.
44	Pritchard A, Tousif S, Wang Y, Hough K, Khan S, Strenkowski J, Chacko BK, Darley-Usmar VM and Deshane JS: Lung tumor Cell-Derived exosomes promote M2 macrophage polarization. Cells. 9:13032020.
45	Khan FH, Reza MJ, Shao YF, Perwez A, Zahra H, Dowlati A and Abbas A: Role of exosomes in lung cancer: A comprehensive insight from immunomodulation to theragnostic applications. Biochim Biophys Acta Rev Cancer. 1877:1887762022.
46	Guo W, Li Y, Pang W and Shen H: Exosomes: A potential therapeutic tool targeting communications between tumor cells and macrophages. Mol Ther. 28:1953–1964. 2020.
47	Bożyk A, Wojas-Krawczyk K, Krawczyk P and Milanowski J: Tumor Microenvironment-A short review of cellular and interaction diversity. Biology (Basel). 11:9292022.
48	Burassakarn A, Srisathaporn S, Pientong C, Wongjampa W, Vatanasapt P, Patarapadungkit N and Ekalaksananan T: Exosomes-carrying Epstein-Barr virus-encoded small RNA-1 induces indoleamine 2, 3-dioxygenase expression in tumor-infiltrating macrophages of oral squamous-cell carcinomas and suppresses T-cell activity by activating RIG-I/IL-6/TNF-α pathway. Oral Oncol. 117:1052792021.
49	Shen Y, Guo D, Weng L, Wang S, Ma Z, Yang Y, Wang P, Wang J and Cai Z: Tumor-derived exosomes educate dendritic cells to promote tumor metastasis via HSP72/HSP105-TLR2/TLR4 pathway. Oncoimmunology. 6:e13625272017.
50	Li X, Liu Y, Zheng S, Zhang T, Wu J, Sun Y, Zhang J and Liu G: Role of exosomes in the immune microenvironment of ovarian cancer. Oncol Lett. 21:3772021.
51	Rubenich DS, Omizzollo N, Szczepański MJ, Reichert TE, Whiteside TL, Ludwig N and Braganhol E: Small extracellular vesicle-mediated bidirectional crosstalk between neutrophils and tumor cells. Cytokine Growth Factor Rev. 61:16–26. 2021.
52	Zhang X, Shi H, Yuan X, Jiang P, Qian H and Xu W: Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration. Mol Cancer. 17:1462018.
53	Shao Q, Deng L, Liu H, Liu Z, Chen J, Jiang F, Yan S and Fu R: Involvement of MM cell-derived exosomes in T lymphocytes immune responses. Oncol Lett. 20:312020.
54	Ferguson Bennit HR, Gonda A, Kabagwira J, Oppegard L, Chi D, Licero Campbell J, De Leon M and Wall NR: Natural killer cell phenotype and functionality affected by exposure to extracellular survivin and Lymphoma-Derived exosomes. Int J Mol Sci. 22:12552021.
55	Papademetrio DL, Garcia MN, Grasso D and Alvarez É: Autophagy-Mediated exosomes as immunomodulators of natural killer cells in pancreatic cancer microenvironment. Front Oncol. 10:6229562021.
56	Luo H, Zhou Y, Zhang J, Zhang Y, Long S, Lin X, Yang A, Duan J, Yang N, Yang Z, et al: NK cell-derived exosomes enhance the anti-tumor effects against ovarian cancer by delivering cisplatin and reactivating NK cell functions. Front Immunol. 13:10876892023.
57	Tumino N, Besi F, Martini S, Di Pace AL, Munari E, Quatrini L, Pelosi A, Fiore PF, Fiscon G, Paci P, et al: Polymorphonuclear Myeloid-Derived suppressor cells are abundant in peripheral blood of cancer patients and suppress natural killer cell Anti-tumor activity. Front Immunol. 12:8030142022.
58	Yan Y, Wang R, Guan W, Qiao M and Wang L: Roles of microRNAs in cancer associated fibroblasts of gastric cancer. Pathol Res Pract. 213:730–736. 2017.
59	Ding X, Xi W, Ji J, Cai Q, Jiang J, Shi M, Yu Y, Zhu Z and Zhang J: HGF derived from cancer-associated fibroblasts promotes vascularization in gastric cancer via PI3K/AKT and ERK1/2 signaling. Oncol Rep. 40:1185–1195. 2018.
60	Ma J, Song X, Xu X and Mou Y: Cancer-Associated-Fibroblasts promote the chemo-resistance in gastric cancer through secreting IL-11 targeting JAK/STAT3/Bcl2 pathway. Cancer Res Treat. 51:194–210. 2019.
61	Wei R, Song J and Liu X, Huo S, Liu C and Liu X: Immunosuppressive MFAP2+ cancer associated fibroblasts conferred unfavorable prognosis and therapeutic resistance in gastric cancer. Cell Oncol (Dordr). Aug 4–2023. View Article : Google Scholar : Epub ahead of print.
62	Lu G, Du R, Dong J, Sun Y, Zhou F, Feng F, Feng B, Han Y and Shang Y: Cancer associated fibroblast derived SLIT2 drives gastric cancer cell metastasis by activating NEK9. Cell Death Dis. 14:4212023.
63	Iha K, Sato A, Tsai HY, Sonoda H, Watabe S, Yoshimura T, Lin MW and Ito E: Gastric cancer cell-derived exosomal GRP78 enhances angiogenesis upon stimulation of vascular endothelial cells. Curr Issues Mol Biol. 44:6145–6157. 2022.
64	Xue X, Huang J, Yu K, Chen X, He Y, Qi D and Wu Y: YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells. BMC Cancer. 20:9962020.
65	Zhou Z, Zhang H, Deng T, Ning T, Liu R, Liu D, Bai M, Ying G and Ba Y: Exosomes Carrying MicroRNA-155 target forkhead Box O3 of endothelial cells and promote angiogenesis in gastric cancer. Mol Ther Oncolytics. 25:2622022.
66	Oya Y, Hayakawa Y and Koike K: Tumor microenvironment in gastric cancers. Cancer Sci. 111:2696–2707. 2020.
67	Hao Y, Zheng C, Wang L, Hu Y, Guo H, Song Q, Zhang H, Zhang Z and Zhang Y: Covalent self-assembled nanoparticles with pH-dependent enhanced tumor retention and drug release for improving tumor therapeutic efficiency. J Mater Chem B. 5:2133–2144. 2017.
68	Zhu KG, Yang J, Zhu Y, Zhu Q, Pan W, Deng S, He Y, Zuo D, Wang P, Han Y and Zhang HY: The microprotein encoded by exosomal lncAKR1C2 promotes gastric cancer lymph node metastasis by regulating fatty acid metabolism. Cell Death Dis. 14:7082023.
69	Wang R, Liang L, Matsumoto M, Iwata K, Umemura A and He F: Reactive Oxygen species and NRF2 signaling, friends or foes in cancer? Biomolecules. 13:3532023.
70	Chen H, Sun Q, Zhang C, She J, Cao S, Cao M, Zhang N, Adiila AV, Zhong J, Yao C, et al: Identification and Validation of CYBB, CD86, and C3AR1 as the key genes related to macrophage infiltration of gastric cancer. Front Mol Biosci. 8:7560852021.
71	Zhao LX, Zhang K, Shen BB and Li JN: Mesenchymal stem cell-derived exosomes for gastrointestinal cancer. World J Gastrointest Oncol. 13:1981–1996. 2021.
72	Tian X, Shen H, Li Z, Wang T and Wang S: Tumor-derived exosomes, myeloid-derived suppressor cells, and tumor microenvironment. J Hematol Oncol. 12:842019.
73	Liu K, Gao X, Kang B, Liu Y, Wang D and Wang Y: The role of tumor stem cell exosomes in cancer invasion and metastasis. Front Oncol. 12:8365482022.
74	da Costa VR, Araldi RP, Vigerelli H, D'Ámelio F, Mendes TB, Gonzaga V, Policíquio B, Colozza-Gama GA, Valverde CW and Kerkis I: Exosomes in the tumor microenvironment: From biology to clinical applications. Cells. 10:26172021.
75	Wang T, Nasser MI, Shen J, Qu S, He Q and Zhao M: Functions of exosomes in the triangular relationship between the tumor, inflammation, and immunity in the tumor microenvironment. J Immunol Res. 2019:41978292019.
76	Lopez K, Lai SWT, Lopez Gonzalez EDJ, Dávila RG and Shuck SC: Extracellular vesicles: A dive into their role in the tumor microenvironment and cancer progression. Front Cell Dev Biol. 11:11545762023.
77	Thakur A, Johnson A, Jacobs E, Zhang K, Chen J, Wei Z, Lian Q and Chen HJ: Energy sources for exosome communication in a cancer microenvironment. Cancers (Basel). 14:16982022.
78	Yan Y, Fu G, Ye Y and Ming L: Exosomes participate in the carcinogenesis and the malignant behavior of gastric cancer. Scand J Gastroenterol. 52:499–504. 2017.
79	Yoon JH, Choi BJ, Nam SW and Park WS: Gastric cancer exosomes contribute to the field cancerization of gastric epithelial cells surrounding gastric cancer. Gastric Cancer. 25:490–502. 2022.
80	Liang ZF, Zhang Y, Guo W, Chen B, Fang S and Qian H: Gastric cancer stem cell-derived exosomes promoted tobacco smoke-triggered development of gastric cancer by inducing the expression of circ670. Med Oncol. 40:242022.
81	Chang L, Gao H, Wang L, Wang N, Zhang S, Zhou X and Yang H: Exosomes derived from miR-1228 overexpressing bone marrow-mesenchymal stem cells promote growth of gastric cancer cells. Aging (Albany NY). 13:11808–11821. 2021.
82	Lin S, Que Y, Que C, Li F, Deng M and Xu D: Exosome miR-3184-5p inhibits gastric cancer growth by targeting XBP1 to regulate the AKT, STAT3, and IRE1 signalling pathways. Asia Pac J Clin Oncol. 19:e27–e38. 2023.
83	Piao HY, Guo S, Wang Y and Zhang J: Exosome-transmitted lncRNA PCGEM1 promotes invasive and metastasis in gastric cancer by maintaining the stability of SNAI1. Clin Transl Oncol. 23:246–256. 2021.
84	Yang H, Zhang H, Ge S, Ning T, Bai M, Li J, Li S, Sun W, Deng T, Zhang L, et al: Exosome-Derived miR-130a activates angiogenesis in gastric cancer by targeting C-MYB in vascular endothelial cells. Mol Ther. 26:2466–2475. 2018.
85	Gu H, Ji R, Zhang X, Wang M, Zhu W, Qian H, Chen Y, Jiang P and Xu W: Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway. Mol Med Rep. 14:3452–3458. 2016.
86	Gao Q, Cui L, Huang C, Zhou C, Chen B, Wang Q, Wang M, Shene B, Xu W and Zhu W: Gastric cancer-derived exosomes induce PD-L1 expression on human bone marrow mesenchymal stem cells through the AKT-c-Myc signal axis. Front Life Sci. 442–451. 2022.
87	Fu H, Yang H, Zhang X, Wang B, Mao J, Li X, Wang M, Zhang B, Sun Z, Qian H and Xu W: Exosomal TRIM3 is a novel marker and therapy target for gastric cancer. J Exp Clin Cancer Res. 37:1622018.
88	Sun Y, Jin J, Jing H, Lu Y, Zhu Q, Shu C, Zhang Q and Jing D: ITIH4 is a novel serum biomarker for early gastric cancer diagnosis. Clin Chim Acta. 523:365–373. 2021.
89	Wang S, He Y, Lu J, Wang Y, Wu X, Yan G, Fang X and Liu B: All-in-One strategy for downstream molecular profiling of tumor-derived exosomes. ACS Appl Mater Interfaces. 14:36341–36352. 2022.
90	Dong Z, Sun X, Xu J, Han X, Xing Z, Wang D, Ge J, Meng L and Xu X: Serum Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) mRNA Protected by exosomes as a potential biomarker for gastric cancer. Med Sci Monit. 25:7770–7783. 2019.
91	Cai C, Zhang H, Zhu Y, Zheng P, Xu Y, Sun J, Zhang M, Lan T, Gu B, Li S and Ma P: Serum exosomal long noncoding RNA pcsk2-2:1 as a potential novel diagnostic biomarker for gastric cancer. OncoTargets Ther. 12:10035–10041. 2019.
92	Joo HS, Jeon HY, Hong EB, Kim HY and Lee JM: Exosomes for the diagnosis and treatment of dementia. Curr Opin Psychiatry. 36:119–125. 2023.
93	Aheget H, Mazini L, Martin F, Belqat B, Marchal JA and Benabdellah K: Exosomes: Their role in pathogenesis, diagnosis and treatment of diseases. Cancers (Basel). 13:842020.
94	Wang J, Sun X, Zhao J, Yang Y, Cai X, Xu J and Cao P: Exosomes: A novel strategy for treatment and prevention of diseases. Front Pharmacol. 8:3002017.
95	Jiang L, Chen W, Ye J and Wang Y: Potential role of exosomes in ischemic stroke treatment. Biomolecules. 115:122022.
96	You D, Kundu S, Schmaier AH, Khorana AA and McCrae KR: Exosome polyphosphate mediates the activation of FXII by cancer cell-derived exosomes. Blood. 132:38002018.
97	Zhang H, Wang Y, Bai M, Wang J, Zhu K, Liu R, Ge S, Li J, Ning T, Deng T, et al: Exosomes serve as nanoparticles to suppress tumor growth and angiogenesis in gastric cancer by delivering hepatocyte growth factor siRNA. Cancer Sci. 109:629–641. 2018.
98	Wang X, Zhang H, Bai M, Ning T, Ge S, Deng T, Liu R, Zhang L, Ying G and Ba Y: Exosomes serve as nanoparticles to deliver Anti-miR-214 to reverse chemoresistance to cisplatin in gastric cancer. Mol Ther. 26:774–783. 2018.