肿瘤微环境在前列腺癌发病机制中的研究进展

doi:10.3760/cma.j.cn371439-20250929-00081

摘要/Abstract

摘要：

前列腺癌是一种高度异质性疾病，其肿瘤微环境中具有复杂的细胞生态系统。肿瘤微环境在前列腺癌的发生与发展进程中发挥着极为关键的作用。鉴于其在支撑肿瘤组织生长方面的重要功能，相关研究正日益聚焦于这一领域。相关研究表明，肿瘤微环境内细胞及其功能的异质性有利于促进更有效的疾病治疗策略的研发，特别是肿瘤组织和宿主细胞在肿瘤微环境中的相互作用与共同进化，能够衍生出新型治疗组合模式，这些组合具备治疗并最终治愈肿瘤的巨大潜力。

关键词: 前列腺肿瘤, 肿瘤微环境, 肿瘤细胞

Abstract:

Prostate cancer is a highly heterogeneous disease with a complex cellular ecosystem in the tumor microenvironment. The tumor microenvironment plays a crucial role in the occurrence and development of prostate cancer. Given its significant function in supporting tumor tissues growth， related research is increasingly focusing on this field. Relevant studies have shown that cellular and functional heterogeneity in the tumor microenvironment can promote the development of more effective disease treatment strategies. In particular， the interaction and co-evolution of tumor tissues and host cells in the tumor microenvironment can lead to novel therapeutic combination models that have great potential for treating and ultimately curing tumors.

Key words: Prostatic neoplasms, Tumor microenvironment, Tumor cells

车禹男, 陈翔, 储旭, 卢道峰, 蒋堃. 肿瘤微环境在前列腺癌发病机制中的研究进展[J]. 国际肿瘤学杂志, 2026, 53(8): 502-507.

Che Yunan, Chen Xiang, Chu Xu, Lu Daofeng, Jiang Kun. Research progress of tumor microenvironment in the pathogenesis of prostate cancer[J]. Journal of International Oncology, 2026, 53(8): 502-507.

参考文献 44

[1]	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[J]. CA Cancer J Clin, 2024, 74(3): 229-263. DOI: 10.3322/caac.21834.
[2]	赵明君, 于春虎. 1990—2019年中国男性泌尿生殖系统肿瘤发病和死亡分析[J]. 国际肿瘤学杂志, 2024, 51(10): 632-638. DOI: 10.3760/cma.j.cn371439-20240509-00106.
[3]	Rebello RJ, Oing C, Knudsen KE, et al. Prostate, cancer[J]. Nat Rev Dis Primers, 2021, 7(1): 9. DOI: 10.1038/s41572-020-00243-0.
[4]	Sun L, Cao XL, Zhou BC, et al. Tumor-associated mesenchymal stem/stromal cells in tumor microenvironment and carcinogenesis[J]. Exp Hematol Oncol, 2025, 14(1): 97. DOI: 10.1186/s40164-025-00688-7. pmid: 40676710
[5]	Ollauri-Ibáñez C, Ayuso-Íñigo B, Pericacho M. Hot and cold tumors: is endoglin (CD105) a potential target for vessel normalization?[J]. Cancers (Basel), 2021, 13(7): 1552. DOI: 10.3390/cancers13071552.
[6]	Leclerc BG, Charlebois R, Chouinard G, et al. CD73 expression is an independent prognostic factor in prostate cancer[J]. Clin Cancer Res, 2016, 22(1): 158-166. DOI: 10.1158/1078-0432.CCR-15-1181. pmid: 26253870
[7]	Gardani CFF, Pedrazza EL, Paz VS, et al. Exploring CD39 and CD73 expression as potential biomarkers in prostate cancer[J]. Pharmaceuticals (Basel), 2023, 16(11): 1619. DOI: 10.3390/ph16111619.
[8]	Xiong Z, Zhuang RL, Yu SL, et al. Cancer-associated fibroblasts regulate mitochondrial metabolism and inhibit chemosensitivity via ANGPTL4-IQGAP1 axis in prostate cancer[J]. J Adv Res, 2025, 75: 663-678. DOI: 10.1016/j.jare.2024.12.003.
[9]	Qin HX, Yang Y, Bo J, et al. SOX9 in prostate cancer is upregulated by cancer-associated fibroblasts to promote tumor progression through HGF/c-Met-FRA1 signaling[J]. FEBS J, 2021, 288(18): 5406-5429. DOI: 10.1111/febs.15816. pmid: 33705609
[10]	Castellón EA, Indo S, Contreras HR. Cancer stemness/epithelial-mesenchymal transition axis influences metastasis and castration resistance in prostate cancer: potential therapeutic target[J]. Int J Mol Sci, 2022, 23(23): 14917. DOI: 10.3390/ijms232314917.
[11]	Lin JQ, Elkon J, Ricart B, et al. Phase Ⅰ study of entinostat in combination with enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer[J]. Oncologist, 2021, 26(12): e2136-e2142. DOI: 10.1002/onco.13957.
[12]	Kfoury Y, Baryawno N, Severe N, et al. Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment[J]. Cancer cell, 2021, 39(11): 1464-1478.e8. DOI: 10.1016/j.ccell.2021.09.005. pmid: 34719426
[13]	Huang RL, Wang SQ, Wang N, et al. CCL5 derived from tumor-associated macrophages promotes prostate cancer stem cells and metastasis via activating β-catenin/STAT3 signaling[J]. Cell Death Dis, 2020, 11(4): 234. DOI: 10.1038/s41419-020-2435-y. pmid: 32300100
[14]	Li XF, Selli C, Zhou HL, et al. Macrophages promote anti-androgen resistance in prostate cancer bone disease[J]. J Exp Med, 2023, 220(4): e20221007. DOI: 10.1084/jem.20221007.
[15]	Masetti M, Carriero R, Portale F, et al. Lipid-loaded tumor-associated macrophages sustain tumor growth and invasiveness in prostate cancer[J]. J Exp Med, 2022, 219(2): e20210564. DOI: 10.1084/jem.20210564.
[16]	Wang C, Peng G, Huang H, et al. Blocking the feedback loop between neuroendocrine differentiation and macrophages improves the therapeutic effects of enzalutamide (MDV3100) on prostate cancer[J]. Clin Cancer Res, 2018, 24(3): 708-723. DOI: 10.1158/1078-0432.CCR-17-2446. pmid: 29191973
[17]	Macías M, García-Cortés Á, Torres M, et al. Characterization of the perioperative changes of exosomal immune-related cytokines induced by prostatectomy in early-stage prostate cancer patients[J]. Cytokine, 2021, 141: 155471. DOI: 10.1016/j.cyto.2021.155471.
[18]	Hirano T. IL-6 in inflammation, autoimmunity and cancer[J]. Int Immunol, 2021, 33(3): 127-148. DOI: 10.1093/intimm/dxaa078. pmid: 33337480
[19]	Peng G, Wang C, Wang HR, et al. Gankyrin-mediated interaction between cancer cells and tumor-associated macrophages facilitates prostate cancer progression and androgen deprivation therapy resistance[J]. Oncoimmunology, 2023, 12(1): 2173422. DOI: 10.1080/2162402X.2023.2173422.
[20]	Adekoya TO, Richardson RM. Cytokines and chemokines as mediators of prostate cancer metastasis[J]. Int J Mol Sci, 2020, 21(12): 4449. DOI: 10.3390/ijms21124449.
[21]	Hawley JE, Pan S, Figg WD, et al. Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy[J]. Prostate, 2020, 80(4): 336-344. DOI: 10.1002/pros.23948. pmid: 31899823
[22]	Midavaine É, Côté J, Sarret P. The multifaceted roles of the chemokines CCL2 and CXCL12 in osteophilic metastatic cancers[J]. Cancer Metastasis Rev, 2021, 40(2): 427-445. DOI: 10.1007/s10555-021-09974-2.
[23]	Armstrong AJ, Geva R, Chung HC, et al. CXCR2 antagonist nava-rixin in combination with pembrolizumab in select advanced solid tumors: a phase 2 randomized trial[J]. Invest New Drugs, 2024, 42(1): 145-159. DOI: 10.1007/s10637-023-01410-2.
[24]	Zhou J, Wu H, Su QX, et al. Impacts of chemokine (C-X-C Motif) receptor 2 C1208T polymorphism on cancer susceptibility[J]. J Immunol Res, 2021, 2021: 8727924. DOI: 10.1155/2021/8727924.
[25]	Shree B, Das K, Sharma V. Emerging role of transforming growth factor-β-regulated long non-coding RNAs in prostate cancer pathogenesis[J]. Cancer Pathog Ther, 2022, 1(3): 195-204. DOI: 10.1016/j.cpt.2022.12.003.
[26]	Narayan V, Barber-Rotenberg JS, Jung IY, et al. PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial[J]. Nat Med, 2022, 28(4): 724-734. DOI: 10.1038/s41591-022-01726-1. pmid: 35314843
[27]	Barata PC, Cooney M, Mendiratta P, et al. Phase Ⅰ/Ⅱ study evaluating the safety and clinical efficacy of temsirolimus and bevacizumab in patients with chemotherapy refractory metastatic castration-resistant prostate cancer[J]. Invest New Drugs, 2019, 37(2): 331-337. DOI: 10.1007/s10637-018-0687-5.
[28]	Sarkar C, Goswami S, Basu S, et al. Angiogenesis inhibition in prostate cancer: an update[J]. Cancers (Basel), 2020, 12(9): 2382. DOI: 10.3390/cancers12092382.
[29]	Moonesi M, Zaka Khosravi S, Molaei Ramshe S, et al. IGF family effects on development, stability, and treatment of hematological malignancies[J]. J Cell Physiol, 2021, 236(6): 4097-4105. DOI: 10.1002/jcp.30156. pmid: 33184857
[30]	Qian F, Huo DZ. Circulating insulin-like growth factor-1 and risk of total and 19 site-specific cancers: cohort study analyses from the UK Biobank[J]. Cancer Epidemiol Biomarkers Prev, 2020, 29(11): 2332-2342. DOI: 10.1158/1055-9965.EPI-20-0743.
[31]	Matsushita M, Fujita K, Hatano K, et al. Connecting the dots between the Gut-IGF-1-prostate axis: a role of IGF-1 in prostate carcinogenesis[J]. Front Endocrinol (Lausanne), 2022, 13: 852382. DOI: 10.3389/fendo.2022.852382.
[32]	Liu GQ, Zhu MG, Zhang MR, et al. Emerging role of IGF-1 in prostate cancer: a promising biomarker and therapeutic target[J]. Cancers (Basel), 2023, 15(4): 1287. DOI: 10.3390/cancers15041287.
[33]	Lin SL, Lin CY, Lee W, et al. Mini review: molecular interpretation of the IGF/IGF-1R axis in cancer treatment and stem cells-based therapy in regenerative medicine[J]. Int J Mol Sci, 2022, 23(19): 11781. DOI: 10.3390/ijms231911781.
[34]	Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update[J]. Nat Rev Cancer, 2012, 12(3): 159-169. DOI: 10.1038/nrc3215. pmid: 22337149
[35]	Karwacki J, Kiełbik A, Szlasa W, et al. Boosting the immune response-combining local and immune therapy for prostate cancer treatment[J]. Cells, 2022, 11(18): 2793. DOI: 10.3390/cells11182793.
[36]	Zhu Q, Wang Y, Liu Y, et al. Prostate transmembrane androgen inducible protein 1 (PMEPA1): regulation and clinical implications[J]. Front Oncol, 2023, 13: 1298660. DOI: 10.3389/fonc.2023.1298660.
[37]	Sharad S, Dobi A, Srivastava S, et al. PMEPA1 gene isoforms: a potential biomarker and therapeutic target in prostate cancer[J]. Biomolecules, 2020, 10(9): 1221. DOI: 10.3390/biom10091221.
[38]	Roudsari NM, Lashgari NA, Momtaz S, et al. Inhibitors of the PI3K/Akt/mTOR pathway in prostate cancer chemoprevention and intervention[J]. Pharmaceutics, 2021, 13(8): 1195. DOI: 10.3390/pharmaceutics13081195.
[39]	Rescigno P, Porta N, Finneran L, et al. Capivasertib in combination with enzalutamide for metastatic castration resistant prostate cancer after docetaxel and abiraterone: results from the randomized phase Ⅱ RE-AKT trial[J]. Eur J Cancer, 2024, 205: 114103. DOI: 10.1016/j.ejca.2024.114103.
[40]	Raith F, O'Donovan DH, Lemos C, et al. Addressing the reciprocal crosstalk between the AR and the PI3K/AKT/mTOR signaling pathways for prostate cancer treatment[J]. Int J Mol Sci, 2023, 24(3): 2289. DOI: 10.3390/ijms24032289.
[41]	Palicelli A, Croci S, Bisagni A, et al. What do we have to know about PD-L1 expression in prostate cancer? A systematic literature review (Part 6): correlation of PD-L1 expression with the status of mismatch repair system, BRCA, PTEN, and other genes[J]. Biomedicines, 2022, 10(2): 236. DOI: 10.3390/biomedicines10020236.
[42]	Adzavon YM, Culig Z, Sun ZJ. Interactions between androgen and IGF1 axes in prostate tumorigenesis[J]. Nat Rev Urol, 2025, 22(5): 268-275. DOI: 10.1038/s41585-024-00942-3.
[43]	Zhao SK, Liao J, Zhang SL, et al. The positive relationship between androgen receptor splice variant-7 expression and the risk of castration-resistant prostate cancer: a cumulative analysis[J]. Front Oncol, 2023, 13: 1053111. DOI: 10.3389/fonc.2023.1053111.
[44]	Srivastava TP, Ajmeriya S, Goel I, et al. Prognostic role of androgen receptor splice variant 7 (AR-V7) in the pathogenesis of breast cancer[J]. BMC Cancer, 2024, 24(1): 1398. DOI: 10.1186/s12885-024-13165-x. pmid: 39538154