肝脏微环境细胞对结肠直肠癌肝转移的作用

摘要/Abstract

摘要：

肝脏是结肠直肠癌最常见的转移部位。肝脏微环境包含了复杂的细胞群体，每种细胞都具备独特的生物学特性和功能，辅以细胞之间的交互作用，共同调节肿瘤微环境，对结肠直肠癌肝转移的发生和发展起到关键作用。深入探索结肠直肠肝转移相关的分子机制，对于理解肿瘤进展、预测转移风险以及开发新的治疗策略至关重要。本文重点从肝脏肿瘤微环境的细胞组成角度出发，探讨了不同细胞类型在肠癌肝转移过程中的作用和影响，旨在为结肠直肠癌肝转移的诊疗提供新的视角和思路。

关键词:结肠直肠癌肝转移,肿瘤微环境,肝星状细胞,肝窦内皮细胞,库普弗细胞,中性粒细胞,巨噬细胞,髓源性抑制细胞

Abstract:

The liver is the most common site of metastasis in patients with colorectal cancer(CRC). The liver microenvironment is a diverse assemblage of cells, which has their own unique biological characteristics and functions, supplemented by the interaction between cells, which jointly regulate the tumor microenvironment and play significant role in the occurrence and development of CRC liver metastasis. Consequently, a thorough investigation of the molecular mechanisms underlying CRC liver metastasis is imperative for comprehension of tumor progression, prediction of metastasis risk, and the development of innovative therapeutic strategy. This paper delved into the cellular constituents of the liver tumor microenvironment, elucidating the roles and influences of diverse cell types in the process of CRC liver metastasis, offering fresh insights and strategies for the diagnosis and management of CRC liver metastasis.

Key words:Colorectal cancer liver metastasis,Tumor microenvironment,Hepatic stellate cell(HepSC),Liver sinusoidal endothelial cell(LSEC),Kupffer cell(KC),Neutrophil,Macrophage,Myeloid-derived suppressor cell(MDSC)

中图分类号:

赵一鸣, 吴棕, 王鲁. 肝脏微环境细胞对结肠直肠癌肝转移的作用[J]. 外科理论与实践, 2024, 29(02): 126-131.

ZHAO Yiming, WU Zong, WANG Lu. The role of liver microenvironment cells in colorectal cancer liver metastasis[J]. Journal of Surgery Concepts & Practice, 2024, 29(02): 126-131.

参考文献41

[1]	SIEGEL R L, WAGLE N S, CERCEK A, et al. Colorectal cancer statistics,2023[J].CA Cancer J Clin,2023,73(3):233-254.
[2]	SIEGEL R L, GIAQUINTO A N, JEMAL A. Cancer statistics, 2024[J].CA Cancer J Clin,2024,74(1):12-49.
[3]	TSILIMIGRAS D I, BRODT P, CLAVIEN P A, et al. Liver metastases[J].Nat Rev Dis Primers,2021,7(1):27. doi:10.1038/s41572-021-00261-6pmid:33859205
[4]	ALI S M, PAWLIK T M, RODRIGUEZ-BIGAS M A, et al. Timing of surgical resection for curative colorectal cancer with liver metastasis[J].Ann Surg Oncol,2018,25(1):32-37. doi:10.1245/s10434-016-5745-7pmid:28224365
[5]	ADAM R, DE GRAMONT A, FIGUERAS J, et al. Mana-ging synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus[J].Cancer Treat Rev,2015,41(9),729-741.
[6]	CHANDRA R, KARALIS J D, LIU C, et al. The colorectal cancer tumor microenvironment and its impact on liver and lung metastasis[J].Cancers(Basel),2021,13(24):6206.
[7]	TSILIMIGRAS D I, HYER J M, BAGANTE F, et al. Resection of colorectal liver metastasis: prognostic impact of tumor burdenvs.KRAS mutational status[J].J Am Coll Surg,2021,232(4):590-598.
[8]	ZHOU H, LIU Z, WANG Y, et al. Colorectal liver metastasis: molecular mechanism and interventional therapy[J].Signal Transduct Target Ther,2022,7(1):70.
[9]	WANG Y, ZHONG X, HE X, et al. Liver metastasis from colorectal cancer: pathogenetic development, immune landscape of the tumour microenvironment and therapeutic approaches[J].J Exp Clin Cancer Res,2023,42(1):177. doi:10.1186/s13046-023-02729-7pmid:37480104
[10]	BRODT P. Role of the microenvironment in liver metastasis: from pre- to prometastatic niches[J].Clin Cancer Res,2016,22(24):5971-5982. pmid:27797969
[11]	VAN DEN EYNDEN G G, MAJEED A W, ILLEMANN M, et al. The multifaceted role of the microenvironment in liver metastasis: biology and clinical implications[J].Cancer Res,2013,73(7):2031-2043. doi:10.1158/0008-5472.CAN-12-3931pmid:23536564
[12]	WISSE E, DE ZANGER R B, CHARELS K, et al. The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse[J].Hepatology,1985,5(4):683-692. doi:10.1002/hep.1840050427pmid:3926620
[13]	LI X, RAMADORI P, PFISTER D, et al. The immunological and metabolic landscape in primary and metastatic liver cancer[J].Nat Rev Cancer,2021,21(9):541-557. doi:10.1038/s41568-021-00383-9pmid:34326518
[14]	RADA M, TSAMCHOE M, KAPELANSKI-LAMOUREUX A, et al. Cancer cells promote phenotypic alterations in hepatocytes at the edge of cancer cell nests to facilitate vessel co-option establishment in colorectal cancer liver metastases[J].Cancers (Basel),2022,14(5):1318.
[15]	IBRAHIM N S, LAZARIS A, RADA M, et al. Angiopoie-tin 1 deficiency in hepatocytes affects the growth of colorectal cancer liver metastases (CRCLM)[J].Cancers (Basel),2019,12(1):35.
[16]	RIDDIOUGH G E, FIFIS T, MURALIDHARAN V, et al. Renin-angiotensin inhibitor, captopril, attenuates growth of patient-derived colorectal liver metastasis organoids[J].Int J Mol Sci,2024,25(6):3282.
[17]	FAN W, CAO D, YANG B, et al. Hepatic prohibitin 1 and methionine adenosyltransferase alpha 1 defend against primary and secondary liver cancer metastasis[J].J Hepatol,2024,80(3):443-453.
[18]	WOHLFEIL S A, GÉRAUD C. Endothelial and tumor-intrinsic mechanisms of hepatic melanoma metastasis[J].J Dtsch Dermatol Ges,2024,22(1):18-21.
[19]	FRIEDMAN S L. Mechanisms of hepatic fibrogenesis[J].Gastroenterology,2008,134(6):1655-1669. doi:10.1053/j.gastro.2008.03.003pmid:18471545
[20]	ZHAO S, MI Y, ZHENG B, et al. Highly-metastatic colorectal cancer cell released miR-181a-5p-rich extracellular vesicles promote liver metastasis by activating hepatic stellate cells and remodelling the tumour microenvironment[J].J Extracell Vesicles,2022,11(1):e12186.
[21]	ZHENG Y, ZHOU R, CAI J, et al. Matrix stiffness triggers lipid metabolic cross-talk between tumor and stromal cells to mediate bevacizumab resistance in colorectal cancer liver metastases[J].Cancer Res,2023,83(21):3577-3592.
[22]	QI M, FAN S, HUANG M, et al. Targeting FAPalpha-expressing hepatic stellate cells overcomes resistance to antiangiogenics in colorectal cancer liver metastasis models[J].J Clin Invest,2022,132(19):e157399.
[42]	HASHIMOTO M, KONDA J D, PERRINO S, et al. Targeting the IGF-axis potentiates immunotherapy for pancreatic ductal adenocarcinoma liver metastases by alte-ring the immunosuppressive microenvironment[J].Mol Cancer Ther,2021,20(12):2469-2482.
[43]	KATOH H, WANG D, DAIKOKU T, et al. CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis[J].Cancer Cell,2013,24(5):631-644. doi:10.1016/j.ccr.2013.10.009pmid:24229710
[44]	KESKINOV A A, SHURIN M R. Myeloid regulatory cells in tumor spreading and metastasis[J].Immunobiology,2015,220(2):236-242. doi:10.1016/j.imbio.2014.07.017pmid:25178934
[45]	SADE-FELDMAN M, KANTERMAN J, ISH-SHALOM E, et al. Tumor necrosis factor-alpha blocks differentiation and enhances suppressive activity of immature myeloid cells during chronic inflammation[J].Immunity,2013,38(3):541-554.
[46]	MILETTE S, HASHIMOTO M, PERRINO S, et al. Sexual dimorphism and the role of estrogen in the immune microenvironment of liver metastases[J].Nat Commun,2019,10(1):5745. doi:10.1038/s41467-019-13571-xpmid:31848339
[47]	CHANG L, XU L, TIAN Y, et al. NLRP6 deficiency suppresses colorectal cancer liver metastasis growth by modulating M-MDSC-induced immunosuppressive microenvironment[J].Biochim Biophys Acta Mol Basis Dis,2024,1870(3):167035.
[23]	CHARLES R, CHOU H S, WANG L, et al. Human hepatic stellate cells inhibit T-cell response through B7-H1 pathway[J].Transplantation,2013,96(1):17-24. doi:10.1097/TP.0b013e318294caaepmid:23756770
[24]	HÖCHST B, SCHILDBERG F A, SAUERBORN P, et al. Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion[J].J Hepatol,2013,59(3):528-535. doi:10.1016/j.jhep.2013.04.033pmid:23665041
[25]	CRISPE I N. Liver antigen-presenting cells[J].J Hepatol,2011,54(2):357-365. doi:10.1016/j.jhep.2010.10.005pmid:21084131
[26]	OU J, PENG Y, DENG J, et al. Endothelial cell-derived fibronectin extra domain A promotes colorectal cancer metastasisviainducing epithelial-mesenchymal transition[J].Carcinogenesis,2014,35(7):1661-1670.
[27]	MARQUEZ J, FERNANDEZ-PIÑEIRO I, ARAÚZO-BRAVO M J, et al. Targeting liver sinusoidal endothelial cells with miR-20a-loaded nanoparticles reduces murine colon cancer metastasis to the liver[J].Int J Cancer,2018,143(3):709-719. doi:10.1002/ijc.31343pmid:29492958
[28]	BENEDICTO A, HERRERO A, ROMAYOR I, et al. Liver sinusoidal endothelial cell ICAM-1 mediated tumor/endothelial crosstalk drives the development of liver metastasis by initiating inflammatory and angiogenic responses[J].Sci Rep,2019,9(1):13111. doi:10.1038/s41598-019-49473-7pmid:31511625
[29]	MATSUMURA H, KONDO T, OGAWA K, et al. Kupffer cells decrease metastasis of colon cancer cells to the liver in the early stage[J].Int J Oncol,2014,45(6):2303-2310. doi:10.3892/ijo.2014.2662pmid:25231346
[30]	KUBES P, JENNE C. Immune responses in the liver[J].Annu Rev Immunol,2018,36:247-277.
[31]	ZHANG Y N, POON W, TAVARES A J, et al. Nanoparticle-liver interactions:cellular uptake and hepatobiliary elimination[J].J Control Release,2016,240:332-348.
[32]	YU X, CHEN L, LIU J, et al. Immune modulation of liver sinusoidal endothelial cells by melittin nanoparticles suppresses liver metastasis[J].Nat Commun,2019,10(1):574. doi:10.1038/s41467-019-08538-xpmid:30718511
[33]	MIZUNO R, KAWADA K, ITATANI Y, et al. The role of tumor-associated neutrophils in colorectal cancer[J].Int J Mol Sci,2019,20(3):529.
[34]	GIESE M A, HIND L E, HUTTENLOCHER A. Neutrophil plasticity in the tumor microenvironment[J].Blood,2019,133(20):2159-2167. doi:10.1182/blood-2018-11-844548pmid:30898857
[35]	CASSETTA L, POLLARD J W. Targeting macrophages: therapeutic approaches in cancer[J].Nat Rev Drug Discov,2018,7(12):887-904.
[36]	COOLS-LARTIGUE J, SPICER J, MCDONALD B, et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis[J].J Clin Invest,2013,123(8):3446-3658.
[37]	YANG L, LIU Q, ZHANG X, et al. DNA of neutrophil extracellular traps promotes cancer metastasisviaCCDC25[J].Nature,2020,583(7814):133-138.
[38]	LI C, CHEN T, LIU J, et al. FGF19-induced inflammatory CAF promoted neutrophil extracellular trap formation in the liver metastasis of colorectal cancer[J].Adv Sci (Weinh),2023,10(24):e2302613.
[39]	KITAMURA T, FUJISHITA T, LOETSCHER P, et al. Inactivation of chemokine (C-C motif) receptor 1 (CCR1) suppresses colon cancer liver metastasis by blocking accumulation of immature myeloid cells in a mouse model[J].Proc Natl Acad Sci U S A,2010,107(29):13063-13068.
[40]	WEI X, YE J, PEI Y, et al. Extracellular vesicles from colorectal cancer cells promote metastasisviathe NOD1 signalling pathway[J].J Extracell Vesicles,2022,11(9):e12264.
[41]	ZHAO L, LIM S Y, GORDON-WEEKS A N, et al. Recruitment of a myeloid cell subset (CD11b/Gr1 mid)viaCCL2/CCR2 promotes the development of colorectal cancer liver metastasis[J].Hepatology,2013,57(2):829-839.