食管癌中肿瘤相关成纤维细胞的异质性及靶向治疗

徐欣瑶, 赵丽娜, 卢佳煜, 张旭旭, 郑春龙, 李家贺, 李玮, 卢强

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重庆医科大学学报 ›› 2024, Vol. 49 ›› Issue (12) : 1550-1555. DOI: 10.13406/j.cnki.cyxb.003684
综述

食管癌中肿瘤相关成纤维细胞的异质性及靶向治疗

作者信息 +

Heterogeneity of cancer-associated fibroblasts in esophageal cancer and targeted therapy

Author information +
History +

摘要

食管癌（esophageal cancer，EC）是一种高侵袭性的恶性肿瘤，具有发现晚、复发率高及预后较差等特点。食管癌的进展与其肿瘤微环境（tumor microenvironment，TME）密切相关。肿瘤相关成纤维细胞（cancer-associated fibroblasts，CAFs）作为TME的关键部分，在癌细胞分泌物、细胞接触信号、机械应力和生理应力等作用下，被募集并重编程，从而表现出异质性。目前，CAFs的异质性提示需要开发针对性的靶向治疗方法，以克服肿瘤微环境中的复杂性和治疗抵抗。未来的研究将更加注重对CAFs异质性的深入理解，以及如何将这些知识转化为临床上的治疗优势。通过识别和功能性地操纵特定的CAF亚群，可以设计出新的治疗策略。为了阐明食管癌中CAFs的复杂性及其作为治疗靶点的潜力，本文综述了近年来关于CAFs的起源、异质性以及其作为靶向治疗的研究进展。

Abstract

Esophageal cancer（EC） is a highly invasive malignant tumor characterized by late identification，a high recurrence rate，and poor prognosis. The progression of EC is closely associated with the tumor microenvironment（TME）. Cancer-associated fibroblasts（CAFs），as a key component of the TME，are recruited and reprogrammed in response to cancer cell secretions，cell contact signals，mechanical stress，and physiological stress，thereby exhibiting heterogeneity. Currently，the heterogeneity of CAFs suggests the need to develop targeted therapeutic approaches to overcome the complexity of the TME and treatment resistance. Future research will focus on a deeper understanding of the heterogeneity of CAFs and how to translate this knowledge into the advantages of clinical treatment. New treatment strategies can be designed by identifying and functionally manipulating the specific subgroups of CAFs. To clarify the complexity of CAFs in EC and their potential as therapeutic targets，this article summarizes the recent research advances in the origin and heterogeneity of CAFs and the role of CAFs in targeted therapy.

关键词

食管癌 / 肿瘤相关成纤维细胞：异质性：化疗

Key words

esophageal cancer / cancer-associated fibroblasts / heterogeneity / chemotherapy

中图分类号

R473.72

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导出引用
徐欣瑶 , 赵丽娜 , 卢佳煜 , 等. 食管癌中肿瘤相关成纤维细胞的异质性及靶向治疗. 重庆医科大学学报. 2024, 49(12): 1550-1555 https://doi.org/10.13406/j.cnki.cyxb.003684
Xu Xinyao, Zhao Lina, Lu Jiayu, et al. Heterogeneity of cancer-associated fibroblasts in esophageal cancer and targeted therapy[J]. Journal of Chongqing Medical University. 2024, 49(12): 1550-1555 https://doi.org/10.13406/j.cnki.cyxb.003684

参考文献

列表( 原文顺序 | 文献年度倒序 | 文中引用次数倒序 ) 可视化分析
1
Zhu HC， Ma X， Ye T，et al. Esophageal cancer in China：Practice and research in the new era[J]. Int J Cancer，2023，152（9）：1741-1751.
本文引用 [1]
2
王建强，邱爱燕，张海文，等. 基质金属蛋白酶抑制剂对人胰腺癌细胞迁移和侵袭的抑制作用[J]. 现代肿瘤医学，2023，31（22）：4153-4157.
Wang JQ， Qiu AY， Zhang HW，et al. Anti-migration and invasion effect of matrix metalloproteinase inhibitor in human pan-creatic cancer cells[J]. J Mod Oncol，2023，31（22）：4153-4157.
本文引用 [1]
3
de Visser KE， Joyce JA. The evolving tumor microenvironment：From cancer initiation to metastatic outgrowth[J]. Cancer Cell，2023，41（3）：374-403.
本文引用 [1]
4
Mao XQ， Xu J， Wang W，et al. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment：new findings and future perspectives[J]. Mol Cancer，2021，20（1）：131.
本文引用 [1]
5
Chhabra Y， Weeraratna AT. Fibroblasts in cancer：Unity in heterogeneity[J]. Cell，2023，186（8）：1580-1609.
本文引用 [1]
6
Niu NN， Shen XQ， Wang Z，et al. Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer[J]. Cancer Cell，2024，42（5）：869-884.
本文引用 [1]
7
Luo H， Xia XY， Huang LB，et al. Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment[J]. Nat Commun，2022，13（1）：6619.
本文引用 [1]
8
Dzobo K， Dandara C. Architecture of cancer-associated fibroblasts in tumor microenvironment：mapping their origins，heterogeneity，and role in cancer therapy resistance[J]. OMICS，2020，24（6）：314-339.
本文引用 [1]
9
Kennel KB， Bozlar M， De Valk AF，et al. Cancer-associated fibroblasts in inflammation and antitumor immunity[J]. Clin Cancer Res，2023，29（6）：1009-1016.
本文引用 [1]
10
Chen YM， Zhu SH， Liu TY，et al. Epithelial cells activate fibroblasts to promote esophageal cancer development[J]. Cancer Cell，2023，41（5）：903-918.
本文引用 [1]
11
Fang LL， Che Y， Zhang CQ，et al. LAMC1 upregulation via TGFβ induces inflammatory cancer-associated fibroblasts in esophageal squamous cell carcinoma via NF-κB-CXCL1-STAT3[J]. Mol Oncol，2021，15（11）：3125-3146.
本文引用 [1]
12
Fang LL， Che Y， Zhang CQ，et al. PLAU directs conversion of fibroblasts to inflammatory cancer-associated fibroblasts，promoting esophageal squamous cell carcinoma progression via uPAR/Akt/NF-κB/IL8 pathway[J]. Cell Death Discov，2021，7（1）：32.
本文引用 [1]
13
Chen J， Wang Y， Zhang WM，et al. Membranous NOX5-derived ROS oxidizes and activates local Src to promote malignancy of tumor cells[J]. Signal Transduct Target Ther，2020，5（1）：139.
本文引用 [1]
14
Chen J， Wang Y， Zhang WM，et al. NOX5 mediates the crosstalk between tumor cells and cancer-associated fibroblasts via regulating cytokine network[J]. Clin Transl Med，2021，11（8）：e472.
本文引用 [2]
15
Nouraee N， van Roosbroeck K， Vasei M，et al. Expression，tissue distribution and function of miR-21 in esophageal squamous cell carcinoma[J]. PLoS One，2013，8（9）：e73009.
本文引用 [1]
16
Qiu HB， Zhang X， Qi JL，et al. Identification and characterization of FGFR2+ hematopoietic stem cell-derived fibrocytes as precursors of cancer-associated fibroblasts induced by esophageal squamous cell carcinoma[J]. J Exp Clin Cancer Res，2022，41（1）：240.
本文引用 [1]
17
Liu XY， Liu YB， Xu JC，et al. Single-cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma[J]. Clin Transl Med，2023，13（3）：e1203.
本文引用 [1]
18
Jia YX， Zhang BF， Zhang CY，et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in esophageal squamous cell carcinoma[J]. Adv Sci，2023，10（7）：e2204565.
本文引用 [1]
19
Dinh HQ， Pan F， Wang G，et al. Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment[J]. Nat Commun，2021，12（1）：7335.
本文引用 [1]
20
Lee YE， Go GY， Koh EY，et al. Synergistic therapeutic combination with a CAF inhibitor enhances CAR-NK-mediated cytotoxicity via reduction of CAF-released IL-6[J]. J Immunother Cancer，2023，11（2）：e006130.
本文引用 [1]
21
Xu WW， Li B， Guan XY，et al. Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression[J]. Nat Commun，2017，8：14399.
本文引用 [1]
22
曾瑞琪，何卫阳，曾铁兵，等. 肿瘤相关成纤维细胞的促瘤作用及其靶向治疗研究进展[J]. 现代肿瘤医学，2024，32（16）：3156-3160.
Zeng RQ， He WY， Zeng TB，et al. Research progress on the tumor-promoting effects of cancer-associated fibroblasts and their targeted therapy[J]. J Mod Oncol，2024，32（16）：3156-3160.
本文引用 [1]
23
Jin Y， Meng QL， Zhang BH，et al. Cancer-associated fibroblasts-derived exosomal miR-3656 promotes the development and progression of esophageal squamous cell carcinoma via the ACAP2/PI3K-AKT signaling pathway[J]. Int J Biol Sci，2021，17（14）：3689-3701.
本文引用 [1]
24
Shimizu M， Koma YI， Sakamoto H，et al. Metallothionein 2A expression in cancer-associated fibroblasts and cancer cells promotes esophageal squamous cell carcinoma progression[J]. Cancers，2021，13（18）：4552.
本文引用 [1]
25
Kashima H， Noma K， Ohara T，et al. Cancer-associated fibroblasts（CAFs） promote the lymph node metastasis of esophageal squamous cell carcinoma[J]. Int J Cancer，2019，144（4）：828-840.
本文引用 [1]
26
Chen C， Yang CB， Tian XY，et al. Downregulation of miR-100-5p in cancer-associated fibroblast-derived exosomes facilitates lymphangiogenesis in esophageal squamous cell carcinoma[J]. Cancer Med，2023，12（13）：14468-14483.
本文引用 [1]
27
Tian BQ， Chen XJ， Zhang HH，et al. Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma[J]. Oncotarget，2017，8（26）：42300-42313.
本文引用 [1]
28
Higashino N， Koma YI， Hosono M，et al. Fibroblast activation protein-positive fibroblasts promote tumor progression through secretion of CCL2 and interleukin-6 in esophageal squamous cell carcinoma[J]. Lab Invest，2019，99（6）：777-792.
本文引用 [1]
29
Miyako S， Koma YI， Nakanishi T，et al. Periostin in cancer-associated fibroblasts promotes esophageal squamous cell carcinoma progression by enhancing cancer and stromal cell migration[J]. Am J Pathol，2024，194（5）：828-848.
本文引用 [1]
30
Huang TX， Tan XY， Huang HS，et al. Targeting cancer-associated fibroblast-secreted WNT2 restores dendritic cell-mediated antitumour immunity[J]. Gut，2022，71（2）：333-344.
本文引用 [1]
31
Liu BL， Zhang BF， Qi JL，et al. Targeting MFGE8 secreted by cancer-associated fibroblasts blocks angiogenesis and metastasis in esophageal squamous cell carcinoma[J]. Proc Natl Acad Sci U S A，2023，120（42）：e2307914120.
本文引用 [2]
32
Chu YY， Fang Y， Wu HT，et al. Vocal fold fibroblasts promote angiogenesis in vocal fold leukoplakia by secreting pro-angiogenic factors[J]. Auris Nasus Larynx，2022，49（6）：1009-1018.
本文引用 [1]
33
Du XL， Xu QP， Pan DY，et al. HIC-5 in cancer-associated fibroblasts contributes to esophageal squamous cell carcinoma progression[J]. Cell Death Dis，2019，10（12）：873.
本文引用 [1]
34
Croft W， Evans RPT， Pearce H，et al. The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy[J]. Mol Cancer，2022，21（1）：200.
本文引用 [1]
35
Chen XJ， Cheng GY， Zhu L，et al. Alarmin S100A8 imparts chemoresistance of esophageal cancer by reprogramming cancer-associated fibroblasts[J]. Cell Rep Med，2024，5（6）：101576.
本文引用 [1]
36
Zhao QT， Huang L， Qin GH，et al. Cancer-associated fibroblasts induce monocytic myeloid-derived suppressor cell generation via IL-6/exosomal miR-21-activated STAT3 signaling to promote cisplatin resistance in esophageal squamous cell carcinoma[J]. Cancer Lett，2021，518：35-48.
本文引用 [1]
37
郑 雨，马 磊，李睿智，等. 细胞外基质硬度对人前列腺癌细胞可塑性调控作用的研究[J]. 精准医学杂志，2024，39（3）：222-225，231.
Zheng Y， Ma L， Li RZ，et al. Effect of extracellular matrix hardness on plasticity of human prostate cancer cells[J]. J Precis Med，2024，39（3）：222-225，231.
本文引用 [1]
38
Yang XY， Chen XJ， Zhang SS，et al. Collagen 1-mediated CXCL1 secretion in tumor cells activates fibroblasts to promote radioresistance of esophageal cancer[J]. Cell Rep，2023，42（10）：113270.
本文引用 [1]
39
邢思远，樊青霞，单争争，等. 食管癌免疫耐受及治疗方法的探索[J]. 肿瘤防治研究，2023，50（12）：1174-1179.
Xing SY， Fan QX， Shan ZZ，et al. Exploration of immune tolerance and treatment for esophageal cancer[J]. Cancer Res Prev Treat，2023，50（12）：1174-1179.
本文引用 [1]
40
Li F， Xin J， Shi Q，et al.Advances in near infrared photoimmunotherapy of tumor[J].Journal of China Pharmaceutical University，2020，51（6）：664-674.
本文引用 [1]
41
Watanabe S， Noma K， Ohara T，et al. Photoimmunotherapy for cancer-associated fibroblasts targeting fibroblast activation protein in human esophageal squamous cell carcinoma[J]. Cancer Biol Ther，2019，20（9）：1234-1248.
本文引用 [1]
42
Katsube R， Noma K， Ohara T，et al. Fibroblast activation protein targeted near infrared photoimmunotherapy（NIR PIT） overcomes therapeutic resistance in human esophageal cancer. Sci Rep，2021，11（1）：1693.
本文引用 [1]
43
Sato H， Noma K， Ohara T，et al. Dual-targeted near-infrared photoimmunotherapy for esophageal cancer and cancer-associated fibroblasts in the tumor microenvironment[J]. Sci Rep，2022，12（1）：20152.
本文引用 [1]

基金

国家自然科学基金资助项目(81872699)
陕西省技术创新引导专项资助项目(2021QFY01-03)
空军军医大学第二附属医院临床研究资助项目(2021LCYJ008)
陕西省重点研发计划资助项目(2024SF-YBXM-112)

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