本刊稿约论文模板电子书
首页 > 过刊浏览>2025年第卷第3期 >426-434. DOI:10.7655/NYDXBNSN240867
PDF HTML阅读 XML下载 导出引用 引用提醒
成纤维细胞在胃黏膜癌变及胃癌药物治疗中的研究进展
作者:
作者单位:

南京医科大学附属无锡人民医院消化内科，南京医科大学无锡医学中心，国家消化系统疾病临床医学研究中心(西安)江苏省分中心，江苏 无锡 214023

中图分类号:

R735.2

基金项目:

江苏省自然科学基金（BK20211039）；无锡市双百拔尖人才项目（BJ2023008）；南京医科大学无锡医学中心专病队列和临床研究项目（WMCC202302）；南京医科大学无锡医学中心重点项目（WMCM202305）


Research progress of fibroblasts in gastric mucosal carcinogenesis and drug therapy of gastric cancer
Author:
  • HAN Jinglüe

    HAN Jinglüe

    Department of Gastroenterology，the Affiliated Wuxi People’s Hospital of Nanjing Medical University，Wuxi Medical Center，Nanjing Medical University，Jiangsu Branch of the National Clinical Research Center for Digestive Diseases （Xi’an），Wuxi 214023 ，China
    在期刊界中查找
    在百度中查找
    在本站中查找
  • AN Fangmei

    AN Fangmei

    Department of Gastroenterology，the Affiliated Wuxi People’s Hospital of Nanjing Medical University，Wuxi Medical Center，Nanjing Medical University，Jiangsu Branch of the National Clinical Research Center for Digestive Diseases （Xi’an），Wuxi 214023 ，China
    在期刊界中查找
    在百度中查找
    在本站中查找
Affiliation:

Department of Gastroenterology，the Affiliated Wuxi People’s Hospital of Nanjing Medical University，Wuxi Medical Center，Nanjing Medical University，Jiangsu Branch of the National Clinical Research Center for Digestive Diseases (Xi’an)，Wuxi 214023 ，China

  • 摘要
    • | |
  • 访问统计
    • |
  • 参考文献 [58]
    • |
  • 相似文献 [20]
    • |
  • 引证文献
    • | |
  • 文章评论
    摘要:

    成纤维细胞在细胞外基质的合成与重塑中发挥重要作用，参与维持组织结构、介导免疫调节、炎症及肿瘤发生等生理病理过程。在胃黏膜癌变前期，成纤维细胞就参与并维持了胃黏膜的萎缩与化生。当胃黏膜癌变后，被激活的成纤维细胞通过与胃癌细胞及肿瘤微环境中的其他组分相互作用，塑造了适合胃癌生长的微环境从而促进胃癌的增殖、侵袭和转移，但作用机制复杂，仍需要进一步探索。同时，成纤维细胞被发现与胃癌的化疗耐药密切相关。因此，以成纤维细胞为靶点的药物可能为癌症治疗提供新的方向，并在降低癌症复发转移风险，减少化疗耐药，改善癌症预后方面发挥重要作用。文章就成纤维细胞促进胃黏膜癌变的作用机制及其在胃癌药物治疗效果评价中作一综述，为成纤维细胞在胃癌发病及治疗中的作用研究提供理论基础。

    Abstract:

    Fibroblasts play important functions in the synthesis and remodeling of extracellular matrix and are involved in physiopathological processes such as maintaining tissue structure，mediating immune regulation，inflammation and tumorigenesis. Fibroblasts participate in and maintain the atrophy and chemotaxis of the gastric mucosa in the precancerous stage. When the gastric mucosa becomes cancerous，the activated fibroblasts interact with gastric cancer cells and other components of the tumor microenvironment，shaping a microenvironment suitable for the growth of gastric cancer and thus promoting gastric cancer proliferation， invasion，and metastasis，but the mechanism of action is complex and needs to be further explored. Meanwhile，fibroblasts have been found to be closely associated with chemoresistance in gastric cancer. Therefore，drugs targeting fibroblasts may provide a new direction for cancer treatment and play an important role in reducing the risk of cancer recurrence and metastasis，decreasing chemoresistance and improving cancer prognosis. In this study，we provide a review on the mechanism of fibroblasts promoting gastric mucosal carcinogenesis and their role in evaluating the effect of gastric cancer drug therapy，in order to provide a theoretical basis for the study of the role of fibroblasts in the pathogenesis and treatment of gastric cancer.

    参考文献
    [1] SMYTH E C，NILSSON M，GRABSCH H I，et al.Gastric cancer[J].Lancet，2020，396：635-648
    [2] SUGANO K，MOSS S F，KUIPERS E J.Gastric intestinal metaplasia：real culprit or innocent bystander as a precancerous condition for gastric cancer?[J].Gastroenterology，2023，165（6）：1352-1366
    [3] CORREA-GALLEGOS D，JIANG D S，RINKEVICH Y.Fibroblasts as confederates of the immune system[J].Immunol Rev，2021，302（1）：147-162
    [4] DE VISSER K E，JOYCE J A.The evolving tumor microenvironment：from cancer initiation to metastatic outgrowth[J].Cancer Cell，2023，41（3）：374-403
    [5] RIMAL R，DESAI P，DAWARE R，et al.Cancer⁃associated fibroblasts：origin，function，imaging，and therapeutic targeting[J].Adv Drug Deliv Rev，2022，189：114504
    [6] CHEN Y，MCANDREWS K M，KALLURI R.Clinical and therapeutic relevance of cancer ⁃associated fibroblasts[J].Nat Rev Clin Oncol，2021，18（12）：792-804
    [7] SHEN X J，ZHANG H，TANG G S，et al.Caveolin⁃1 is a modulator of fibroblast activation and a potential biomarker for gastric cancer[J].Int J Biol Sci，2015，11（4）：370-379
    [8] 孙宇，刘毅强，冯国双，等.转化生长因子β1在萎缩性胃炎发生中的作用[J].北京大学学报（医学版），2009，41（6）：635-639.SUN Y，LIU Y Q，FENG G S，et al.Role of transforming growth factor β1 in the development of atrophic gastritis[J].Journal of Peking University（Health Sciences），2009，41（6）：635-639
    [9] WANG R P，SONG S M，QIN J J，et al.Evolution of immune and stromal cell states and ecotypes during gastric adenocarcinoma progression[J].Cancer Cell，2023，41（8）：1407-1426
    [10] TSUBOSAKA A，KOMURA D，KAKIUCHI M，et al.Stomach encyclopedia：combined single ⁃cell and spatial tran-scriptomics reveal cell diversity and homeostatic regulation of human stomach[J].Cell Rep，2023，42（10）：113236
    [11] KRZYSIEK ⁃MACZKA G，WROBEL T，TARGOSZ A，et al.Helicobacter pylori⁃activated gastric fibroblasts induce epithelial-mesenchymal transition of gastric epithelial cells in vitro in a TGF ⁃β⁃dependent manner[J].Helico-bacter，2019，24（5）：e12653
    [12] LI J，LI X J，ZHANG Z，et al.Helicobacter pylori promotes gastric fibroblast proliferation and migration by expulsing exosomal miR ⁃124⁃3p[J].Microbes Infect，2024，26（1/2）：105236
    [13] KRZYSIEK⁃MACZKA G，TARGOSZ A，PTAK⁃BELOWS-KA A，et al.Molecular alterations in fibroblasts exposed to Helicobacter pylori：a missing link in bacterial inflammation progressing into gastric carcinogenesis?[J].J Physiol Pharmacol，2013，64（1）：77-87
    [14] YAMAMOTO Y，KASASHIMA H，FUKUI Y，et al.The heterogeneity of cancer-associated fibroblast subpopulations：their origins，biomarkers，and roles in the tumor microenvironment[J].Cancer Sci，2023，114（1）：16-24
    [15] LIN H，CAO X Y，WANG Y，et al.Mutual activation between cancer-associated fibroblasts and cancer cells facilitates growth and progression of gastric cancer[J].Int J Clin Exp Pathol，2020，13（10）：2691-2700
    [16] GU J J，LI X C，ZHAO L，et al.The role of PKM2 nuclear translocation in the constant activation of the NF ⁃ κB signaling pathway in cancer-associated fibroblasts[J].Cell Death Dis，2021，12（4）：291
    [17] REINFELD B I，MADDEN M Z，WOLF M M，et al.Cell-programmed nutrient partitioning in the tumour microenvironment[J].Nature，2021，593（7858）：282-288
    [18] OYA Y，HAYAKAWA Y，KOIKE K.Tumor microenvironment in gastric cancers[J].Cancer Sci，2020，111（8）：2696-2707
    [19] ZHOU Q，WU X Y，WANG X F，et al.The reciprocal interaction between tumor cells and activated fibroblasts mediated by TNF ⁃ α/IL ⁃ 33/ST2L signaling promotes gastric cancer metastasis[J].Oncogene，2020，39（7）：1414-1428
    [20] ROGERS S，ZHANG C T，ANAGNOSTIDIS V，et al.Cancer⁃associated fibroblasts influence Wnt/PCP signaling in gastric cancer cells by cytoneme-based dissemination of ROR2[J].Proc Natl Acad Sci U S A，2023，120（39）：e2217612120
    [21] LABERNADIE A，KATO T，BRUGUÉS A，et al.A mechanically active heterotypic E ⁃cadherin/N ⁃cadherin adhesion enables fibroblasts to drive cancer cell invasion[J].Nat Cell Biol，2017，19（3）：224-237
    [22] ROJAS A，ARAYA P，GONZALEZ I，et al.Gastric tumor microenvironment[J].Adv Exp Med Biol，2020，1226：23-35
    [23] WU C Q，LI D M，CHENG X，et al.Downregulation of cancer⁃associated fibroblast exosome⁃derived miR⁃29b⁃1⁃5p restrains vasculogenic mimicry and apoptosis while accelerating migration and invasion of gastric cancer cells via immunoglobulin domain ⁃containing 1/zonula occluden⁃1 axis[J].Cell Cycle，2023，22（17）：1807-1826
    [24] XU G F，ZHANG B，YE J H，et al.Exosomal miRNA⁃139 in cancer-associated fibroblasts inhibits gastric cancer progression by repressing MMP11 expression[J].Int J Biol Sci，2019，15（11）：2320-2329
    [25] HARPER J，SAINSON R C.Regulation of the anti⁃tumour immune response by cancer-associated fibroblasts[J].Semin Cancer Biol，2014，25：69-77
    [26] CASSETTA L，POLLARD J W.A timeline of tumour⁃associated macrophage biology[J].Nat Rev Cancer，2023，23（4）：238-257
    [27] HERRERA M，HERRERA A，DOMÍNGUEZ G，et al.Cancer⁃associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients[J].Cancer Sci，2013，104（4）：437-444
    [28] PAN Y Y，YU Y D，WANG X J，et al.Tumor⁃associated macrophages in tumor immunity[J].Front Immunol，2020，11：583084
    [29] QUANTE M，TU S P，TOMITA H，et al.Bone marrow⁃derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth[J].Cancer Cell，2011，19（2）：257-272
    [30] TAN B H，SHI X J，ZHANG J，et al.Inhibition of rspo-Lgr4 facilitates checkpoint blockade therapy by switching macrophage polarization[J].Cancer Res，2018，78（17）：4929-4942
    [31] LI D D，XIA L Y，HUANG P，et al.Cancer⁃associated fibroblast-secreted IGFBP7 promotes gastric cancer by enhancing tumor associated macrophage infiltration via FGF2/FGFR1/PI3K/AKT axis[J].Cell Death Discov，2023，9（1）：17
    [32] GORDON S R，MAUTE R L，DULKEN B W，et al.PD⁃1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity[J].Nature，2017，545（7655）：495-499
    [33] GOK YAVUZ B，GUNAYDIN G，GEDIK M E，et al.Cancer associated fibroblasts sculpt tumour microenvironment by recruiting monocytes and inducing immunosuppressive PD⁃1+ TAMs[J].Sci Rep，2019，9（1）：3172
    [34] YANG X G，LIN Y L，SHI Y H，et al.FAP promotes immunosuppression by cancer-associated fibroblasts in the tumor microenvironment via STAT3⁃CCL2 signaling[J].Cancer Res，2016，76（14）：4124-4135
    [35] BOURHIS M，PALLE J，GALY-FAUROUX I，et al.Direct and indirect modulation of T cells by VEGF-A counteracted by anti ⁃angiogenic treatment[J].Front Im-munol，2021，12：616837
    [36] SONG M J，HE J Y，PAN Q Z，et al.Cancer⁃associated fibroblast⁃mediated cellular crosstalk supports hepatocellular carcinoma progression[J].Hepatology，2021，73（5）：1717-1735
    [37] ELLEM S J，TAYLOR R A，FURIC L，et al.A pro⁃tumou-rigenic loop at the human prostate tumour interface orchestrated by oestrogen，CXCL12 and mast cell recruitment[J].J Pathol，2014，234（1）：86-98
    [38] YANG F C，CHEN S，CLEGG T，et al.Nf1 +/- mast cells induce neurofibroma like phenotypes through secreted TGF⁃beta signaling[J].Hum Mol Genet，2006，15（16）：2421-2437
    [39] BAE W J，KIM S，AHN J M，et al.Estrogen-responsive cancer⁃associated fibroblasts promote invasive property of gastric cancer in a paracrine manner via CD147 production[J].FASEB J，2022，36（11）：e22597
    [40] ZHANG H Y，DENG T，LIU R，et al.CAF secreted miR⁃ 522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer[J].Mol Cancer，2020，19（1）：43
    [41] YAO L Z，HOU J Y，WU X Y，et al.Cancer⁃associated fibroblasts impair the cytotoxic function of NK cells in gastric cancer by inducing ferroptosisvia iron regulation[J].Redox Biol，2023，67：102923
    [42] LIN X，KANG K，CHEN P，et al.Regulatory mechanisms of PD⁃1/PDL1 in cancers[J].Mol Cancer，2024，23（1）：108
    [43] MU L S，YU W T，SU H L，et al.Relationship between the expressions of PDL1 and tumour-associated fibroblasts in gastric cancer[J].Artif Cells Nanomed Biotech-nol，2019，47（1）：1036-1042
    [44] LI Z Q，ZHOU J W，ZHANG J J，et al.Cancer⁃associated fibroblasts promote PDL1 expression in mice cancer cells via secreting CXCL5[J].Int J Cancer，2019，145（7）：1946-1957
    [45] INOUE C，MIKI Y，SAITO R，et al.PD ⁃L1 induction by cancer⁃associated fibroblast⁃derived factors in lung adenocarcinoma cells[J].Cancers，2019，11（9）：1257
    [46] GONG J，LIN Y Y，ZHANG H Q，et al.Reprogramming of lipid metabolism in cancer⁃associated fibroblasts potentiates migration of colorectal cancer cells[J].Cell Death Dis，2020，11（4）：267
    [47] 中华人民共和国国家卫生健康委员会医政医管局.胃癌诊疗指南（2022年版）[J].中华消化外科杂志，2022，21（9）：1137-1164.Medical Affairs Bureau of the National Health Commission of the People’s Republic of China.Clinical practice guidelines for gastric cancer（2022）[J].Chinese Journal of Digestive Surgery，2022，21（9）：1137-1164
    [48] WEI R Y，SONG J Q，LIU X J，et al.Immunosuppressive MFAP2 + cancer associated fibroblasts conferred unfavorable prognosis and therapeutic resistance in gastric cancer[J].Cell Oncol，2024，47（1）：55-68
    [49] JIN Z J，LU Y F，WU X Y，et al.The crosstalk between tumor cells and activated fibroblasts mediated by lactate/BDNF/TrkB signaling promotes acquired resistance to anlotinib in human gastric cancer[J].Redox Biol，2021，46：102076
    [50] SHITARA K，ÖZGÜROĞLU M，BANG Y J，et al.Pembro-lizumab versus paclitaxel for previously treated，advanced gastric or gastro⁃oesophageal junction cancer（KEYNOTE⁃ 061）：a randomised，open⁃label，controlled，phase 3 trial[J].Lancet，2018，392（10142）：123-133
    [51] YOU T T，TANG H，WU W J，et al.Postnsecretion by extracellular matrix cancer-associated fibroblasts（eCAFs）correlates with poor icbresponse viamacrophage chemotaxis activation of Akt signaling pathway in gastric cancer[J].Aging Dis，2023，14（6）：2177-2192
    [52] QIN Q，YU R，ERIKSSON J E，et al.Cancer⁃associated fibroblasts in pancreatic ductal adenocarcinoma therapy：challenges and opportunities[J].Cancer Lett，2024，591：216859
    [53] WEI J W，WANG M X，LI G X.Cancer⁃associated fibroblasts，and clinicopathological characteristics and prognosis of gastric cancer：a systematic review and meta⁃analysis[J].Front Oncol，2023，13：1048922
    [54] NAKAMURA Y，KINOSHITA J，YAMAGUCHI T，et al.Crosstalk between cancer-associated fibroblasts and immune cells in peritoneal metastasis：inhibition in the migration of M2 macrophages and mast cells by tranilast[J].Gastric Cancer，2022，25（3）：515-526
    [55] CHEN G X，YU C X，TANG Z C，et al.Metformin suppresses gastric cancer progression through calmodulin⁃like protein 3 secreted from tumor-associated fibroblasts[J].Oncol Rep，2019，41（1）：405-414
    [56] BAE C A，HAM I H，OH H J，et al.Inhibiting the GAS6/AXL axis suppresses tumor progression by blocking the interaction between cancer-associated fibroblasts and cancer cells in gastric carcinoma[J].Gastric Cancer，2020，23（5）：824-836
    [57] OGAWA T，KIKUCHI S，TABUCHI M，et al.Modulation of p53 expression in cancer⁃associated fibroblasts prevents peritoneal metastasis of gastric cancer[J].Mol Ther Oncolytics，2022，25：249-261
    [58] WANG Z F，MA D G，WANG L，et al.Paeoniflorin inhibits migration⁃and invasion⁃promoting capacities of gastric cancer associated fibroblasts[J].Chin J Integr Med，2019，25（11）：837-844
    引证文献
    网友评论
    网友评论
    分享到微博
    发 布
引用本文

韩经略,安方梅.成纤维细胞在胃黏膜癌变及胃癌药物治疗中的研究进展[J].南京医科大学学报（自然科学版）,2025,(3):426-434

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2024-08-19
  • 在线发布日期: 2025-03-17

友情链接 Links

技术支持：北京勤云科技发展有限公司
关闭