- 1. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, P. R. China;
- 2. Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing 100029, P. R. China;
Inhibiting metastasis is the key to the treatment of malignant tumors. During the development of tumors, the microenvironment plays a significant role, and hypoxia is one of its important characteristics. Exosomes, as an important component of the microenvironment, connect tumor cells with the hypoxic microenvironment and mediate information exchange between cells. Tumor cells secrete more exosomes than normal cells, and hypoxia further stimulates their release. Hypoxia-induced tumor-derived exosomes carry stable genetic material and play a key regulatory role in promoting tumor proliferation, establishing a pre-metastasis microenvironment, and accelerating angiogenesis. This article comprehensively expounds the mechanism by which tumor-derived exosomes regulate tumor proliferation and metastasis in a hypoxic microenvironment, which has potential clinical significance.
Copyright ? the editorial department of West China Medical Journal of West China Medical Publisher. All rights reserved
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- 3. 張赟, 王小凡. 腫瘤微環境調控癌癥發生發展的研究概述. 中國科學: 生命科學, 2022, 52(9): 1377-1390.
- 4. de Visser KE, Joyce JA. The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth. Cancer Cell, 2023, 41(3): 374-403.
- 5. Roma-Rodrigues C, Mendes R, Baptista V P, et al. Targeting tumor microenvironment for cancer therapy. Int J Mol Sci, 2019, 20(4): 840.
- 6. Boussadia Z, Zanetti C, Parolini I. Role of microenvironmental acidity and tumor exosomes in cancer immunomodulation. Transl Cancer Res, 2020, 9(9): 5775-5786.
- 7. Kyriazi AA, Karaglani M, Agelaki S, et al. Intratumoral microbiome: foe or friend in reshaping the tumor microenvironment landscape?. Cells, 2024, 13(15): 1279-1279.
- 8. 楊一烽, 孫鑫穎, 沈欣桐, 等. 外泌體源性 miRNAs 在肺癌發生發展中的作用. 生物化學與生物物理進展, 2020, 47(3): 188-198.
- 9. 馬苑, 付秀華, 王立紅. 腫瘤缺氧微環境的研究進展. 癌癥進展, 2020, 18(2): 109-112, 147.
- 10. Brizel DM, Scully SP, Harrelson JM, et al. Tumor oxygenation predicts forthe likelihood of distant metastases in human soft tissue sarcoma. Cancer Res, 1996, 56(5): 941-943.
- 11. Le QT, Chen E, Salim A, et al. An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers. Clin Cancer Res, 2006, 12(5): 1507-1514.
- 12. Chen Z, Han F, Du Y, et al. Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther, 2023, 8(1): 70.
- 13. Weinberg RA. The biology of cancer. 2nd ed. New York, NY: Garland Science, Taylor & Francis Group, 2013.
- 14. 秦承東, 任正剛, 湯釗猷. 缺氧微環境在腫瘤進展中的作用. 腫瘤, 2016, 36(1): 96-102.
- 15. H?ckel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst, 2001, 93(4): 266-276.
- 16. Thomlinson RH, Gray LH. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer, 1955, 9(4): 539-549.
- 17. Zhang TQ, Lv QY, Jin WL. The cellular-centered view of hypoxia tumor microenvironment: molecular mechanisms and therapeutic interventions. Biochim Biophys Acta Rev Cancer, 2024, 1879(5): 189137.
- 18. 王維媛, 李斑斑, 陳晨, 等. 缺氧在腫瘤發病機制中的研究進展. 中華臨床醫師雜志(電子版), 2015, 9(22): 4197-4201.
- 19. He G, Peng X, Wei S, et al. Exosomes in the hypoxic TME: from release, uptake and biofunctions to clinical applications. Mol Cancer, 2022, 21(1): 19.
- 20. Chen X, Zhou H, Lv J. The importance of hypoxia-related to hemoglobin concentration in breast cancer. Cell Biochem Biophys, 2024, 82(3): 1893-1906.
- 21. 胡飛翔, 李袁靜, 蔡明, 等. 基于 EPR 實現對乳腺癌在化療中氧分壓變化的監測及其機制的探討. 腫瘤, 2014, 34(10): 902-907.
- 22. 朱宏, 施瑞華. 缺氧誘導因子與腫瘤血管生成. 國外醫學(腫瘤學分冊), 2004(8): 591-594.
- 23. Zhao Y, Xing C, Deng Y, et al. HIF-1α signaling: essential roles in tumorigenesis and implications in targeted therapies. Genes Dis, 2024, 11(1): 234-251.
- 24. Nicolini A, Ferrari P. Involvement of tumor immune microenvironment metabolic reprogramming in colorectal cancer progression, immune escape, and response to immunotherapy. Front Immunol, 2024, 15: 1353787.
- 25. Warburg O. On the Origin of Cancer Cells. Science, 1956, 123(3191): 309-314.
- 26. Liu J, Wang Y, Tian M, et al. O-GlcNAcylation of ATP-citrate lyase couples glucose supply to lipogenesis for rapid tumor cell proliferation. Proc Natl Acad Sci U S A, 2024, 121(42): e2402674121.
- 27. Lin R, Tao R, Gao X, et al. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell, 2013, 51(4): 506-518.
- 28. Liu R, Ju G, Lu Y, et al. Inhibition of glutamine synthetase enhances hepatocellular carcinoma radiosensitivity through ROS-induced excessive mitophagy. Mol Biol Rep, 2025, 53(1): 5.
- 29. Wang Y, Wu H, Hu X. Quantification of the inputs and outputs of serine and glycine metabolism in cancer cells. Arch Biochem Biophys, 2025, 768: 110367.
- 30. Tang H, Huang X, Wang J, et al. circKIF4A acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer. Mol Cancer, 2019, 18(1): 23.
- 31. Ye F, Gao G, Zou Y, et al. circFBXW7 inhibits malignant progression by sponging mir-197-3p and encoding a 185-aa protein in triple-negative breast cancer. Mol Ther Nucleic Acids, 2019, 18: 88-98.
- 32. Saxena K, Jolly MK, Balamurugan K. Hypoxia, partial EMT and collective migration: emerging culprits in metastasis. Transl Oncol, 2020, 13(11): 100845.
- 33. Miettinen PJ, Ebner R, Lopez AR, et al. TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. J Cell Biol, 1994, 127(6 Pt 2): 2021-2036.
- 34. Sahlgren C, Gustafsson MV, Jin S, et al. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci U S A, 2008, 105(17): 6392-6397.
- 35. Wang Y, Jia J, Wang F, et al. Pre-metastatic niche: formation, characteristics and therapeutic implication. Signal Transduct Target Ther, 2024, 9(1): 236.
- 36. 茆春國, 鄧波. 肺癌循環腫瘤細胞侵襲轉移機制的研究進展. 中國肺癌雜志, 2020, 23(3): 189-195.
- 37. Magar AG, Morya VK, Kwak MK, et al. A Molecular Perspective on HIF-1α and angiogenic stimulator networks and their role in solid tumors: an update. Int J Mol Sci, 2024, 25(6): 3313.
- 38. Zhao J, Du F, Luo Y, et al. The emerging role of hypoxia-inducible factor-2 involved in chemo/radioresistance in solid tumors. Cancer Treat Rev, 2015, 41(7): 623-633.
- 39. Trams EG, Lauter CJ, Salem N Jr, et al. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta, 1981, 645(1): 63-70.
- 40. Chen YF, Luh F, Ho YS, et al. Exosomes: a review of biologic function, diagnostic and targeted therapy applications, and clinical trials. J Biomed Sci, 2024, 31(1): 67.
- 41. Jiang C, Zhang N, Hu X, et al. Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms. Mol Cancer, 2021, 20(1): 117.
- 42. 楊碩, 楊清玲, 陳昌杰. 腫瘤微環境中外泌體在腫瘤發生發展中作用及機制. 分子診斷與治療雜志, 2020, 12(3): 396-400.
- 43. 鄒洪波, 鄔紅, 許川. 外泌體在肺癌診斷及治療中的研究進展. 中國肺癌雜志, 2016, 19(11): 778-783.
- 44. Camussi G, Deregibus MC, Bruno S, et al. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int, 2010, 78(9): 838-848.
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