肿瘤源性外泌体在口腔鳞状细胞癌中的研究进展

doi:10.13591/j.cnki.kqyx.2025.06.013

摘要/Abstract

摘要：

口腔鳞状细胞癌是常见的头颈部恶性肿瘤,早期手术可取得良好效果,但大多数患者在初诊时已出现颈部淋巴结转移,虽然手术结合放疗或化疗可延缓疾病的进展,但总体预后效果仍不理想,尤其是 Ⅲ/Ⅳ期患者的长期生存率并没有提高。外泌体作为细胞间通信中的关键微泡,包含大量的核酸、蛋白质和脂质等生物分子。肿瘤来源外泌体在调控肿瘤微环境中起着关键作用。本文关于口腔鳞癌中肿瘤来源外泌体对肿瘤增殖、转移、免疫调节、诊断、治疗等进行综述,以期为口腔癌的早期诊断和治疗提供新的思路。

关键词: 肿瘤源性外泌体, 口腔鳞癌, 交互作用, 诊断, 治疗, 预后

Abstract:

Oral squamous cell carcinoma is a common malignant tumor of the head and neck. Early surgery can achieve good results, but most patients have cervical lymph node metastasis at the time of initial diagnosis. Although surgery combined with radiotherapy or chemotherapy can delay the progression of the disease, the overall prognosis is still not ideal. Especially in patients at stage Ⅲ / Ⅳ, the long-term survival rate has not improved. As a key microbubble in intercellular communication, exosomes contain a large number of biological molecules such as nucleic acids, proteins and lipids. Tumor-derived exosomes play a key role in regulating the tumor microenvironment. This article reviews the effects of tumor-derived exosomes on tumor proliferation, metastasis, immune regulation, diagnosis and treatment in oral squamous cell carcinoma, in order to provide new ideas for early diagnosis and treatment of oral cancer.

Key words: tumor-derived exosomes, oral squamous cell carcinoma, interaction, diagnosis, treatment, prognosis

中图分类号:

R782

周兴安, 德乐黑·巴特尔, 武旭, 马宏宇, 夏凤君, 申铁兵, 尚多. 肿瘤源性外泌体在口腔鳞状细胞癌中的研究进展[J]. 口腔医学, 2025, 45(6): 465-469.

ZHOU Xing’an, DELEHEI Bateer, WU Xu, MA Hongyu, XIA Fengjun, SHEN Tiebing, SHANG Duo. Research progress of tumor-derived exosomes in oral squamous cell carcinoma[J]. Stomatology, 2025, 45(6): 465-469.

参考文献 38

[1]	Shang QH, Jiang YC, Wan ZX, et al. The clinical implication and translational research of OSCC differentiation[J]. Br J Cancer, 2024, 130(4): 660-670.
[2]	Vatsa PP, Jindal Y, Bhadwalkar J, et al. Role of epigenetics in OSCC: An understanding above genetics[J]. Med Oncol, 2023, 40(4): 122. doi: 10.1007/s12032-023-01992-0 pmid: 36941511
[3]	Krylova SV, Feng DR. The machinery of exosomes: Biogenesis, release, and uptake[J]. Int J Mol Sci, 2023, 24(2): 1337.
[4]	Sahu S, Routray S. Assessing the analytical efficacy of TEX in diagnosing oral cancer using a systematic review approach[J]. J Oral Pathol Med, 2021, 50(2): 123-128. doi: 10.1111/jop.13126 pmid: 33184963
[5]	Wan MH, Ning B, Spiegel S, et al. Tumor-derived exosomes (TDEs): How to avoid the sting in the tail[J]. Med Res Rev, 2020, 40(1): 385-412. doi: 10.1002/med.21623 pmid: 31318078
[6]	Mondal J, Pillarisetti S, Junnuthula V, et al. Hybrid exosomes, exosome-like nanovesicles and engineered exosomes for therapeutic applications[J]. J Control Release, 2023, 353: 1127-1149.
[7]	徐英娇, 王姗. 唾液外泌体在口腔鳞状细胞癌的研究进展[J]. 口腔医学, 2022, 42(7): 664-667, 672.
[8]	Boussadia Z, Zanetti C, Parolini I. Role of microenvironmental acidity and tumor exosomes in cancer immunomodulation[J]. Transl Cancer Res, 2020, 9(9): 5775-5786. doi: 10.21037/tcr.2020.03.69 pmid: 35117938
[9]	Kalele K, Nyahatkar S, Mirgh D, et al. Exosomes: A cutting-edge theranostics tool for oral cancer[J]. ACS Appl Bio Mater, 2024, 7(3): 1400-1415.
[10]	Li L, Li C, Wang SX, et al. Exosomes derived from hypoxic oral squamous cell carcinoma cells deliver miR-21 to normoxic cells to elicit a prometastatic phenotype[J]. Cancer Res, 2016, 76(7): 1770-1780. doi: 10.1158/0008-5472.CAN-15-1625 pmid: 26992424
[11]	Song Q, Yu H, Cheng YD, et al. Bladder cancer-derived exosomal KRT6B promotes invasion and metastasis by inducing EMT and regulating the immune microenvironment[J]. J Transl Med, 2022, 20(1): 308. doi: 10.1186/s12967-022-03508-2 pmid: 35794606
[12]	Li YY, Tao YW, Gao S, et al. Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p[J]. EBio Medicine, 2018, 36: 209-220.
[13]	Guo HJ, Jiang WD, Huang SH, et al. Serum exosome-derived biomarkers for the early detection of oral squamous cell carcinoma[J]. Mol Cell Biochem, 2021, 476(12): 4435-4447. doi: 10.1007/s11010-021-04254-7 pmid: 34468926
[14]	Zhou JW, Tang ZW, Gao SY, et al. Tumor-associated macrophages: Recent insights and therapies[J]. Front Oncol, 2020, 10: 188. doi: 10.3389/fonc.2020.00188 pmid: 32161718
[15]	Pradhan R, Paul S, Acharya SS, et al. Nano formulated Resveratrol inhibits PD-L1 in oral cancer cells by deregulating the association between tumor associated macrophages and cancer associated fibroblasts through IL-6/JAK2/STAT3 signaling axis[J]. J Nutr Biochem, 2024, 125: 109568.
[16]	Pang X, Wang SS, Zhang M, et al. Correction to: OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway[J]. Cancer Immunol Immunother, 2022, 71(2): 505-506.
[17]	Cai JH, Qiao B, Gao N, et al. Oral squamous cell carcinoma-derived exosomes promote M2 subtype macrophage polarization mediated by exosome-enclosed miR-29a-3p[J]. Am J Physiol Cell Physiol, 2019, 316(5): C731-C740.
[18]	Paskeh MDA, Entezari M, Mirzaei S, et al. Emerging role of exosomes in cancer progression and tumor microenvironment remodeling[J]. J Hematol Oncol, 2022, 15(1): 83.
[19]	Xu ZJ, Chen Y, Ma L, et al. Role of exosomal non-coding RNAs from tumor cells and tumor-associated macrophages in the tumor microenvironment[J]. Mol Ther, 2022, 30(10): 3133-3154. doi: 10.1016/j.ymthe.2022.01.046 pmid: 35405312
[20]	Alipoor SD, Mortaz E, Varahram M, et al. The potential biomarkers and immunological effects of tumor-derived exosomes in lung cancer[J]. Front Immunol, 2018, 9: 819. doi: 10.3389/fimmu.2018.00819 pmid: 29720982
[21]	Naseri M, Bozorgmehr M, Zöller M, et al. Tumor-derived exosomes: The next generation of promising cell-free vaccines in cancer immunotherapy[J]. Oncoimmunology, 2020, 9(1): 1779991.
[22]	Theodoraki MN, Yerneni SS, Hoffmann TK, et al. Clinical significance of PD-L1⁺ exosomes in plasma of head and neck cancer patients[J]. Clin Cancer Res, 2018, 24(4): 896-905.
[23]	Zhu XQ, Qin X, Wang XN, et al. Oral cancer cell-derived exosomes modulate natural killer cell activity by regulating the receptors on these cells[J]. Int J Mol Med, 2020, 46(6): 2115-2125.
[24]	Chen YY, Li ZY, Liang JF, et al. CircRNA has_circ_0069313 induced OSCC immunity escape by miR-325-3p-Foxp3 axes in both OSCC cells and Treg cells[J]. Aging, 2022, 14(10): 4376-4389.
[25]	Qin X, Guo HY, Wang XN, et al. Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5[J]. Genome Biol, 2019, 20(1): 12. doi: 10.1186/s13059-018-1604-0 pmid: 30642385
[26]	Zheng Y, Song A, Zhou Y, et al. Identification of extracellular vesicles-transported miRNAs in Erlotinib-resistant head and neck squamous cell carcinoma[J]. J Cell Commun Signal, 2020, 14(4): 389-402.
[27]	Gao F, Han JJ, Wang Y, et al. Circ_0109291 promotes cisplatin resistance of oral squamous cell carcinoma by sponging miR-188-3p to increase ABCB1 expression[J]. Cancer Biother Radiopharm, 2022, 37(4): 233-245.
[28]	Yuan Y, Wang ZY, Chen MQ, et al. Macrophage-derived exosomal miR-31-5p promotes oral squamous cell carcinoma tumourigenesis through the large tumor suppressor 2-mediated hippo signalling pathway[J]. J Biomed Nanotechnol, 2021, 17(5): 822-837. doi: 10.1166/jbn.2021.3066 pmid: 34082869
[29]	Faur CI, Roman RC, Jurj A, et al. Salivary exosomal microRNA-486-5p and microRNA-10b-5p in oral and oropharyngeal squamous cell carcinoma[J]. Medicina, 2022, 58(10): 1478.
[30]	Lin XJ, Wu WZ, Ying YK, et al. MicroRNA-31: A pivotal oncogenic factor in oral squamous cell carcinoma[J]. Cell Death Discov, 2022, 8(1): 140. doi: 10.1038/s41420-022-00948-z pmid: 35351880
[31]	Li CP, Zhou Y, Liu JJ, et al. Potential markers from serum-purified exosomes for detecting oral squamous cell carcinoma metastasis[J]. Cancer Epidemiol Biomarkers Prev, 2019, 28(10): 1668-1681.
[32]	Lu J, Liu QH, Wang F, et al. Exosomal miR-9 inhibits angiogenesis by targeting MDK and regulating PDK/AKT pathway in nasopharyngeal carcinoma[J]. J Exp Clin Cancer Res, 2018, 37(1): 147. doi: 10.1186/s13046-018-0814-3 pmid: 30001734
[33]	Li M, Yin SY, Xu AN, et al. Synergistic phototherapy-molecular targeted therapy combined with tumor exosome nanoparticles for oral squamous cell carcinoma treatment[J]. Pharmaceutics, 2023, 16(1): 33.
[34]	Xie C, Du LY, Guo FY, et al. Exosomes derived from microRNA-101-3p-overexpressing human bone marrow mesenchymal stem cells suppress oral cancer cell proliferation, invasion, and migration[J]. Mol Cell Biochem, 2019, 458(1/2): 11-26.
[35]	Kamerkar S, Leng CR, Burenkova O, et al. Exosome-mediated genetic reprogramming of tumor-associated macrophages by exoASO-STAT6 leads to potent monotherapy antitumor activity[J]. Sci Adv, 2022, 8(7): eabj7002.
[36]	Liang YJ, Duan L, Lu JP, et al. Engineering exosomes for targeted drug delivery[J]. Theranostics, 2021, 11(7): 3183-3195. doi: 10.7150/thno.52570 pmid: 33537081
[37]	Yong TY, Zhang XQ, Bie NN, et al. Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy[J]. Nat Commun, 2019, 10(1): 3838. doi: 10.1038/s41467-019-11718-4 pmid: 31444335
[38]	Solomon MC, Chandrashekar C, Kulkarni S, et al. Exosomes: Mediators of cellular communication in potentially malignant oral lesions and head and neck cancers[J]. F1000 Res, 2023, 12: 58.