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河南中医药大学 中医药科学研究院,河南省中医方证信号传导重点实验室, 河南省中医方证信号传导国际联合实验室,郑州 450046
Received:19 April 2021,
Published Online:09 November 2021,
Published:20 February 2022
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江始源,司富春,王文彬等.食管癌肿瘤微环境中的癌相关细胞研究进展[J].中国实验方剂学杂志,2022,28(04):262-270.
JIANG Shi-yuan,SI Fu-chun,WANG Wen-bin,et al.Cancer Associated Cells in Tumor Microenvironment of Esophageal Carcinoma: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(04):262-270.
江始源,司富春,王文彬等.食管癌肿瘤微环境中的癌相关细胞研究进展[J].中国实验方剂学杂志,2022,28(04):262-270. DOI: 10.13422/j.cnki.syfjx.20220193.
JIANG Shi-yuan,SI Fu-chun,WANG Wen-bin,et al.Cancer Associated Cells in Tumor Microenvironment of Esophageal Carcinoma: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(04):262-270. DOI: 10.13422/j.cnki.syfjx.20220193.
食管癌是致死率较高的恶性肿瘤之一,全球范围内每年有近57万人死于食管癌,且这一数字逐年攀升。近年来,尽管针对食管癌的治疗方案不断精进,但由于治疗过程中耐药性的产生及患者机体耐受度的不同,食管癌的总体5年生存率仍然不足20%。肿瘤微环境(TME)是以肿瘤细胞为核心的多种细胞及相关成分构成的一种乏氧、酸中毒、慢性炎症及免疫抑制的微环境,对肿瘤的发展起着重要的推动作用。研究发现,TME中的肿瘤相关成纤维细胞、肿瘤相关巨噬细胞、髓源性抑制细胞及调节性T细胞等能通过分泌细胞因子、激活促炎通路等途径促进癌细胞增殖、迁移、侵袭、淋巴结转移,并通过诱导癌细胞耐药性的产生及逃避免疫抑制从而促进癌症进展。由于TME中的癌相关细胞在遗传上比癌细胞更稳定、突变较少,产生耐药性的机会更低,因此通过调控TME,靶向TME中的癌相关细胞是癌症治疗的一个新的研究方向。中药具有多成分、多靶点的优势,能通过多途径参与调控TME,降低TME中癌相关细胞的数量、抑制其与癌细胞之间的串话、恢复免疫细胞功能等,是调控TME及靶向TME中癌相关细胞药物研发的重要来源。该文通过对食管癌TME中癌相关细胞的作用及目前以TME中癌相关细胞为靶向的中药应用进行综述,以期为食管癌TME靶向药物的研发提供参考。
Esophageal carcinoma is one of the malignant tumors with a high mortality rate, accounting for nearly 570,000 cancer deaths worldwide annually, and this number is increasing year by year. In recent years, despite the continuous improvement of treatment programs for esophageal carcinoma, the overall five-year survival rate of esophageal carcinoma is still less than 20% due to the development of drug resistance and the tolerance of patients during the treatment process. Tumor microenvironment (TME) is composed of various cells and related components with tumor cells as the core and featured by hypoxia, acidosis, chronic inflammation and immunosuppression, which plays an important role in the progression of tumors. Studies have found that tumor-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor cells and regulatory T cells in TME can promote the proliferation, migration, invasion, and lymph node metastasis of cancer cells by secreting cytokines and activating pro-inflammatory pathways, and promote cancer progression by inducing the drug resistance of cancer cells and evading immunosuppression. Because cancer-associated cells in TME are genetically more stable than cancer cells, have fewer mutations and have lower chance of drug resistance, targeting cancer-associated cells in TME by regulating TME is a new research direction of cancer therapy. Traditional Chinese medicine has the advantages of multi-component and multi-target. It can participate in the regulation of TME through multiple ways, reduce the number of cancer-associated cells in TME, inhibit crosstalk between TME and cancer cells, and restore immune cell function. It is an important source for the regulation of TME and the research and development of drugs targeting cancer-associated cells in TME. In this paper, the role of cancer-associated cells in the TME of esophageal cancer and the current application of traditional Chinese medicine targeting cancer-associated cells in TME are reviewed, so as to provide reference for the research and development of TME targeted drugs for esophageal carcinoma.
BRAY F , FERLAY J , SOERJOMATARAM I , et al . Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin , 2018 , 68 ( 6 ): 394 - 424 .
MALHOTRA A , SHARMA U , PUHAN S , et al . Stabilization of miRNAs in esophageal cancer contributes to radioresistance and limits efficacy of therapy [J]. Biochimie , 2019 , 156 : 148 - 157 .
WU X , HU W , LU L , et al . Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment [J]. Acta Pharm Sin B , 2019 , 9 ( 2 ): 203 - 219 .
YANG L V . Tumor microenvironment and metabolism [J]. Int J Mol Sci , 2017 , 18 ( 12 ): 2729 .
LIN E W , KARAKASHEVA T A , HICKS P D , et al . The tumor microenvironment in esophageal cancer [J]. Oncogene , 2016 , 35 ( 41 ): 5337 - 5349 .
CHEN X , SONG E . Turning foes to friends:targeting cancer-associated fibroblasts [J]. Nat Rev Drug Discov , 2019 , 18 ( 2 ): 99 - 115 .
ERDOGAN B , WEBB D J . Cancer-associated fibroblasts modulate growth factor signaling and extracellular matrix remodeling to regulate tumor metastasis [J]. Biochem Soc Trans , 2017 , 45 ( 1 ): 229 - 236 .
KAI F , DRAIN A P , WEAVER V M . The extracellular matrix modulates the metastatic journey [J]. Dev Cell , 2019 , 49 ( 3 ): 332 - 346 .
DONGRE A , WEINBERG R A . New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer [J]. Nat Rev Mol Cell Biol , 2019 , 20 ( 2 ): 69 - 84 .
ZHAO G , LI H , GUO Q , et al . Exosomal sonic hedgehog derived from cancer-associated fibroblasts promotes proliferation and migration of esophageal squamous cell carcinoma [J]. Cancer Med , 2020 , 9 ( 7 ): 2500 - 2513 .
TIAN B , CHEN X , ZHANG H , 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 .
UNDERWOOD T J , HAYDEN A L , DEROUET M , et al . Cancer-associated fibroblasts predict poor outcome and promote periostin-dependent invasion in oesophageal adenocarcinoma [J]. J Pathol , 2015 , 235 ( 3 ): 466 - 477 .
DU X , XU Q , PAN D , et al . HIC-5 in cancer-associated fibroblasts contributes to esophageal squamous cell carcinoma progression [J]. Cell Death Dis , 2019 , 10 ( 12 ): 873 .
KARAKASHEVA T A , LIN E W , TANG Q , et al . IL-6 mediates cross-talk between tumor cells and activated fibroblasts in the tumor microenvironment [J]. Cancer Res , 2018 , 78 ( 17 ): 4957 - 4970 .
YEO S Y , HA S Y , LEE K W , et al . Twist1 is highly expressed in cancer-associated fibroblasts of esophageal squamous cell carcinoma with a prognostic significance [J]. Oncotarget , 2017 , 8 ( 39 ): 65265 - 65280 .
CHENG Y , WANG K , MA W , et al . Cancer-associated fibroblasts are associated with poor prognosis in esophageal squamous cell carcinoma after surgery [J]. Int J Clin Exp Med , 2015 , 8 ( 2 ): 1896 - 1903 .
HA S Y , YEO S Y , XUAN Y H , et al . The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma [J]. PLoS One , 2014 , 9 ( 6 ): e99955 .
GOLDSTEIN M , KASTAN M B . The DNA damage response:implications for tumor responses to radiation and chemotherapy [J]. Annu Rev Med , 2015 , 66 : 129 - 143 .
CUI Q , WANG J Q , ASSARAF Y G , et al . Modulating ROS to overcome multidrug resistance in cancer [J]. Drug Resist Updat , 2018 , 41 : 1 - 25 .
ZHANG H , YUE J , JIANG Z , et al . CAF-secreted CXCL1 conferred radioresistance by regulating DNA damage response in a ROS-dependent manner in esophageal squamous cell carcinoma [J]. Cell Death Dis , 2017 , 8 ( 5 ): e2790 .
ZHANG H , HUA Y , JIANG Z , et al . Cancer-associated fibroblast-promoted lncRNA DNM3OS confers radioresistance by regulating DNA damage response in esophageal squamous cell carcinoma [J]. Clin Cancer Res , 2019 , 25 ( 6 ): 1989 - 2000 .
ZHANG H , XIE C , YUE J , et al . Cancer-associated fibroblasts mediated chemoresistance by a FOXO1/TGFbeta1 signaling loop in esophageal squamous cell carcinoma [J]. Mol Carcinog , 2017 , 56 ( 3 ): 1150 - 1163 .
EBBING E A , VAN DER ZALM A P , STEINS A , et al . Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma [J]. Proc Natl Acad Sci U S A , 2019 , 116 ( 6 ): 2237 - 2242 .
THONGCHOT S , FERRARESI A , VIDONI C , et al . Resveratrol interrupts the pro-invasive communication between cancer associated fibroblasts and cholangiocarcinoma cells [J]. Cancer Lett , 2018 , 430 : 160 - 171 .
DU Y , LONG Q , ZHANG L , et al . Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1alpha signaling [J]. Int J Oncol , 2015 , 47 ( 6 ): 2064 - 2072 .
BUHRMANN C , KRAEHE P , LUEDERS C , et al . Curcumin suppresses crosstalk between colon cancer stem cells and stromal fibroblasts in the tumor microenvironment:potential role of EMT [J]. PLoS One , 2014 , 9 ( 9 ): e107514 .
DAUER P , ZHAO X , GUPTA V K , et al . Inactivation of cancer-associated-fibroblasts disrupts oncogenic signaling in pancreatic cancer cells and promotes its regression [J]. Cancer Res , 2018 , 78 ( 5 ): 1321 - 1333 .
WANG Z , MA D , WANG C , et al . Triptonide inhibits the pathological functions of gastric cancer-associated fibroblasts [J]. Biomed Pharmacother , 2017 , 96 : 757 - 767 .
WANG Z F , MA D G , ZHU Z , et al . Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts [J]. World J Gastroenterol , 2017 , 23 ( 48 ): 8512 - 8525 .
阮善明 , 沈敏鹤 , 林红 , 等 . 解毒三根汤干预肿瘤相关成纤维细胞及抑制结肠癌侵袭转移的实验研究 [J]. 中国中西医结合杂志 , 2013 , 33 ( 9 ): 1242 - 1246 .
阮善明 , 缪昊均 , 严卿莹 , 等 . 解毒三根汤调节肿瘤相关成纤维细胞Sirt1-NF- κ B途径抗结肠癌侵袭转移 [J]. 中华中医药杂志 , 2015 , 30 ( 9 ): 3082 - 3086 .
阮善明 , 孙钰 , 张恺 , 等 . 解毒三根汤调节肿瘤相关成纤维细胞抗结肠癌侵袭转移及其对 α -SMA、Sirt1、Ki67的影响 [J]. 浙江中医药大学学报 , 2016 , 40 ( 3 ): 184 - 189 .
CHEN L , QU C , CHEN H , et al . Chinese herbal medicine suppresses invasion-promoting capacity of cancer-associated fibroblasts in pancreatic cancer [J]. PLoS One , 2014 , 9 ( 4 ): e96177 .
URAKAWA N , UTSUNOMIYA S , NISHIO M , et al . GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and ERK pathways [J]. Lab Invest , 2015 , 95 ( 5 ): 491 - 503 .
OKAMOTO M , KOMA Y I , KODAMA T , et al . Growth differentiation factor 15 promotes progression of esophageal squamous cell carcinoma via TGF-beta type Ⅱ receptor activation [J]. Pathobiology , 2020 , 87 ( 2 ): 100 - 113 .
WANG P , XU L J , QIN J J , et al . MicroRNA-155 inversely correlates with esophageal cancer progression through regulating tumor-associated macrophage FGF2 expression [J]. Biochem Biophys Res Commun , 2018 , 503 ( 2 ): 452 - 458 .
TAKASE N , KOMA Y , URAKAWA N , et al . NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of esophageal cancer regulates the survival and migration of tumor-associated macrophages and cancer cells [J]. Cancer Lett , 2016 , 380 ( 1 ): 47 - 58 .
LIU J , LI C , ZHANG L , et al . Association of tumour-associated macrophages with cancer cell EMT,invasion,and metastasis of Kazakh oesophageal squamous cell cancer [J]. Diagn Pathol , 2019 , 14 ( 1 ): 55 .
SUN M M , HE L L , ZHANG H X , et al . The synergistic effect of esophageal squamous cell carcinoma KYSE150 cells and M2 macrophages on lymphatic endothelial cells [J]. Am J Transl Res , 2017 , 9 ( 11 ): 5105 - 5115 .
YANG H , ZHANG Q , XU M , et al . CCL2-CCR2 axis recruits tumor associated macrophages to induce immune evasion through PD-1 signaling in esophageal carcinogenesis [J]. Mol Cancer , 2020 , 19 ( 1 ): 41 .
YAGI T , BABA Y , OKADOME K , et al . Tumour-associated macrophages are associated with poor prognosis and programmed death ligand 1 expression in oesophageal cancer [J]. Eur J Cancer , 2019 , 111 : 38 - 49 .
LU Y , GUO L , DING G . PD1 + tumor associated macrophages predict poor prognosis of locally advanced esophageal squamous cell carcinoma [J]. Future Oncol , 2019 , 15 ( 35 ): 4019 - 4030 .
LIN J , LI Q , CHEN H , et al . Hedyotis diffusa Willd. extract suppresses proliferation and induces apoptosis via IL-6-inducible STAT3 pathway inactivation in human colorectal cancer cells [J]. Oncol Lett , 2015 , 9 ( 4 ): 1962 - 1970 .
WANG B , ZHENG X , LIU J , et al . Osthole inhibits pancreatic cancer progression by directly exerting negative effects on cancer cells and attenuating tumor-infiltrating M2 macrophages [J]. J Pharmacol Sci , 2018 , 137 ( 3 ): 290 - 298 .
JIANG Y X , CHEN Y , YANG Y , et al . Screening five Qi-tonifying herbs on M2 phenotype macrophages [J]. Evid Based Complement Alternat Med , 2019 , doi: 10.1155/2019/9549315 http://dx.doi.org/10.1155/2019/9549315 .
HE J , YIN P , XU K . Effect and molecular mechanisms of traditional Chinese medicine on tumor targeting tumor-associated macrophages [J]. Drug Des Devel Ther , 2020 , 14 : 907 - 919 .
LI H , HUANG N , ZHU W , et al . Modulation the crosstalk between tumor-associated macrophages and non-small cell lung cancer to inhibit tumor migration and invasion by ginsenoside Rh 2 [J]. BMC Cancer , 2018 , 18 ( 1 ): 579 .
GUO Q , LI J , LIN H . Effect and molecular mechanisms of traditional Chinese medicine on regulating tumor immunosuppressive microenvironment [J]. Biomed Res Int , 2015 , doi: 10.1155/2015/261620 http://dx.doi.org/10.1155/2015/261620 .
姜涛 , 钱钧 , 朱伟 , 等 . 加味黄芪建中汤通过IL-33介导肿瘤相关巨噬细胞极化的研究 [J]. 中华中医药杂志 , 2019 , 34 ( 9 ): 4294 - 4297 .
WU J , ZHANG X X , ZOU X , et al . The effect of Jianpi Yangzheng Xiaozheng Decoction and its components on gastric cancer [J]. J Ethnopharmacol , 2019 , 235 : 56 - 64 .
KARAKASHEVA T A , WALDRON T J , ERUSLANOV E , et al . CD38-expressing myeloid-derived suppressor cells promote tumor growth in a murine model of esophageal cancer [J]. Cancer Res , 2015 , 75 ( 19 ): 4074 - 4085 .
LI P , CHEN X , QIN G , et al . Maelstrom directs myeloid-derived suppressor cells to promote esophageal squamous cell carcinoma progression via activation of the Akt1/RelA/IL8 signaling pathway [J]. Cancer Immunol Res , 2018 , 6 ( 10 ): 1246 - 1259 .
XU J , PENG Y , YANG M , et al . Increased levels of myeloid-derived suppressor cells in esophageal cancer patients is associated with the complication of sepsis [J]. Biomed Pharmacother , 2020 , 125 : 109864 .
ZHANG W , HE W , SHI X , et al . An Asparagus polysaccharide fraction inhibits MDSCs by inducing apoptosis through toll-like receptor 4 [J]. Phytother Res , 2018 , 32 ( 7 ): 1297 - 1303 .
ZHOU J , WU J , CHEN X , et al . Icariin and its derivative,ICT,exert anti-inflammatory,anti-tumor effects,and modulate myeloid derived suppressive cells (MDSCs) functions [J]. Int Immunopharmacol , 2011 , 11 ( 7 ): 890 - 898 .
MAO D , FENG L , GONG H . The Antitumor and immunomodulatory effect of Yanghe decoction in breast cancer is related to the modulation of the JAK/STAT signaling pathway [J]. Evid Based Complement Alternat Med , 2018 , 2018 : 8460526 .
LU Y T , LI J , QI X , et al . Effects of Shugan Jianpi Formula (疏肝健脾方) on myeloid-derived suppression cells-mediated depression breast cancer mice [J]. Chin J Integr Med , 2017 , 23 ( 6 ): 453 - 460 .
王敏 , 刘沈林 , 吴坚 , 等 . 益气健脾化瘀方联合5-FU对MFC荷瘤小鼠皮下移植瘤的生长及免疫功能的影响 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 6 ): 65 - 72 .
SHEVACH E M , THORNTON A M . tTregs,pTregs,and iTregs:similarities and differences [J]. Immunol Rev , 2014 , 259 ( 1 ): 88 - 102 .
WEI T , ZHONG W , LI Q . Role of heterogeneous regulatory T cells in the tumor microenvironment [J]. Pharmacol Res , 2020 , 153 : 104659 .
SARHAN D , HIPPEN K L , LEMIRE A , et al . Adaptive NK cells resist regulatory T-cell suppression driven by IL37 [J]. Cancer Immunol Res , 2018 , 6 ( 7 ): 766 - 775 .
胡玉平 , 周海云 , 黄巧玲 , 等 . 丹皮酚对FSL-1与IL-4共刺激诱导树突状细胞成熟及细胞因子表达的影响 [J]. 中国临床药理学与治疗学 , 2019 , 24 ( 1 ): 14 - 19 .
ZHU J , ZHANG Y , SHEN Y , et al . Lycium barbarum polysaccharides induce Toll-like receptor 2- and 4-mediated phenotypic and functional maturation of murine dendritic cells via activation of NF-kappaB [J]. Mol Med Rep , 2013 , 8 ( 4 ): 1216 - 1220 .
HUYAN T , LI Q , YANG H , et al . Protective effect of polysaccharides on simulated microgravity-induced functional inhibition of human NK cells [J]. Carbohydr Polym , 2014 , 101 : 819 - 827 .
师林 , 黄圆圆 , 柯斌 . 加味龟鹿二仙胶汤联合顺铂对Lewis肺癌小鼠耐药相关基因及IL-7介导的Wnt/ β -catenin信号通路的影响 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 18 ): 66 - 72 .
张召杨 , 孙增涛 , 王霖 . 益气温阳法联合顺铂对荷瘤小鼠调节性T细胞的影响 [J]. 世界中医药 , 2021 , 16 ( 14 ): 2110 - 2114 .
杨国良 , 胡丹丹 , 杨玮 . 益气养阴方联合化疗抑制Lewis肺癌移植小鼠肿瘤生长的疗效与机制 [J]. 中华中医药学刊 , 2016 , 34 ( 1 ): 151 - 156 .
林颖 , 邓宇琳 , 王菊勇 . 补肾益肺解毒法对Lewis肺癌小鼠CD4 + CD25 + 调节性T细胞、Foxp3及B7-H3的影响 [J]. 河南中医 , 2017 , 37 ( 11 ): 1911 - 1916 .
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