白血病抑制因子在胰腺导管腺癌中的作用

谢亚兴; 史晨光; 刘晓欢; 马艳波

doi:10.3969/j.issn.1001-5256.2021.12.053

白血病抑制因子在胰腺导管腺癌中的作用

DOI: 10.3969/j.issn.1001-5256.2021.12.053

1.
山西医科大学第一临床医学院，太原 030000
2.
山西医科大学第一医院普通外科，太原 030000

详细信息

通信作者:
马艳波，15103418205@163.com

中图分类号: R735.9
计量
- 文章访问数: 712
- HTML全文浏览量: 72
- PDF下载量: 39
- 被引次数: 0
出版历程
- 收稿日期: 2021-04-21
- 录用日期: 2021-05-13
- 出版日期: 2021-12-20

Role of leukemia inhibitory factor in pancreatic ductal adenocarcinoma

1.
The First Clinical Medical College of Shanxi Medical University, Taiyuan 030000, China
2.
Department of General Surgery, The First Hospital of Shanxi Medical University, Taiyuan 030000, China

摘要

摘要: 胰腺导管腺癌是一种高度侵袭性的消化系统恶性肿瘤，其预后极差。白血病抑制因子是IL-6家族的重要成员，可调节细胞的分化、生长和更新等多个生理过程。基于文献证据对白血病抑制因子在胰腺导管腺癌中的作用机制及白细胞抑制因子靶向治疗的研究进展进行综述，分析表明白血病抑制因子在胰腺导管腺癌的发展、免疫逃逸、化疗抵抗等过程中都起着重要作用，并逐渐成为胰腺导管腺癌潜在的生物标志物和治疗靶点。
- 癌, 胰腺管 /
- 白血病抑制因子 /
- 病理过程
Abstract: Pancreatic ductal adenocarcinoma is a highly invasive malignant tumor of the digestive system with an extremely poor prognosis. Leukemia inhibitory factor is an important member of the interleukin-6 family and can regulate multiple physiological processes such as cell differentiation, growth, and renewing. This article reviews the mechanism of action of leukemia inhibitory factor in pancreatic ductal adenocarcinoma and the research advances in leukocyte inhibitory factor-targeted therapy based on literature evidence, and the analysis shows that leukemia inhibitory factor plays an important role in the progression, immune escape, and chemotherapy resistance of pancreatic ductal adenocarcinoma and may gradually become a potential biomarker and therapeutic target for pancreatic ductal adenocarcinoma.
- Carcinoma, Pancreatic Ductal /
- Leukemia Inhibitory Factor /
- Pathologic Processes

HTML全文

图 1 LIF的JAK/STAT3信号通路

下载: 全尺寸图片幻灯片

参考文献(35)

[1]	SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30. DOI: 10.3322/caac.21590.
[2]	National Health Commission of the People's Republic of China. Diagnosis, management, and treatment of pancreatic adenocarcinoma (V2018)[J]. J Clin Hepatol, 2019, 35(2): 281-293. DOI: 10.3969/j.issn.1001-5256.2019.02.009. 中华人民共和国国家卫生健康委员会. 胰腺癌诊疗规范(2018年版)[J]. 临床肝胆病杂志, 2019, 35(2): 281-293. DOI: 10.3969/j.issn.1001-5256.2019.02.009.
[3]	MURAKAMI M, KAMIMURA D, HIRANO T. Pleiotropy and specificity: Insights from the interleukin 6 family of cytokines[J]. Immunity, 2019, 50(4): 812-831. DOI: 10.1016/j.immuni.2019.03.027.
[4]	JONES SA, JENKINS BJ. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer[J]. Nat Rev Immunol, 2018, 18(12): 773-789. DOI: 10.1038/s41577-018-0066-7.
[5]	GULLUOGLU S, SAHIN M, TUYSUZ EC, et al. Leukemia inhibitory factor promotes aggressiveness of chordoma[J]. Oncol Res, 2017, 25(7): 1177-1188. DOI: 10.3727/096504017X14874349473815.
[6]	NICOLA NA, BABON JJ. Leukemia inhibitory factor (LIF)[J]. Cytokine Growth Factor Rev, 2015, 26(5): 533-544. DOI: 10.1016/j.cytogfr.2015.07.001.
[7]	XIA Y, ZHANG YL, YU C, et al. YAP/TEAD co-activator regulated pluripotency and chemoresistance in ovarian cancer initiated cells[J]. PLoS One, 2014, 9(11): e109575. DOI: 10.1371/journal.pone.0109575.
[8]	MCLEAN K, TAN L, BOLLAND DE, et al. Leukemia inhibitory factor functions in parallel with interleukin-6 to promote ovarian cancer growth[J]. Oncogene, 2019, 38(9): 1576-1584. DOI: 10.1038/s41388-018-0523-6.
[9]	PICCINNI MP, SCALETTI C, VULTAGGIO A, et al. Defective production of LIF, M-CSF and Th2-type cytokines by T cells at fetomaternal interface is associated with pregnancy loss[J]. J Reprod Immunol, 2001, 52(1-2): 35-43. DOI: 10.1016/s0165-0378(01)00111-5.
[10]	METCALFE SM, WATSON TJ, SHUREY S, et al. Leukemia inhibitory factor is linked to regulatory transplantation tolerance[J]. Transplantation, 2005, 79(6): 726-730. DOI: 10.1097/01.tp.0000149324.42994.38.
[11]	SILVER JS, HUNTER CA. gp130 at the nexus of inflammation, autoimmunity, and cancer[J]. J Leukoc Biol, 2010, 88(6): 1145-1156. DOI: 10.1189/jlb.0410217.
[12]	LIGORIO M, SIL S, MALAGON-LOPEZ J, et al. Stromal microenvironment shapes the intratumoral architecture of pancreatic cancer[J]. Cell, 2019, 178(1): 160-175. e27. DOI: 10.1016/j.cell.2019.05.012.
[13]	PASCUAL-GARCíA M, BONFILL-TEIXIDOR E, PLANAS-RIGOL E, et al. LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8⁺ T cell tumor-infiltration impairing anti-PD1 therapy[J]. Nat Commun, 2019, 10(1): 2416. DOI: 10.1038/s41467-019-10369-9.
[14]	GAO W, THOMPSON L, ZHOU Q, et al. Treg versus Th17 lymphocyte lineages are cross-regulated by LIF versus IL-6[J]. Cell Cycle, 2009, 8(9): 1444-1450. DOI: 10.4161/cc.8.9.8348.
[15]	MOHAN V, DAS A, SAGI I. Emerging roles of ECM remodeling processes in cancer[J]. Semin Cancer Biol, 2020, 62: 192-200. DOI: 10.1016/j.semcancer.2019.09.004.
[16]	GIUSSANI M, TRIULZI T, SOZZI G, et al. Tumor extracellular matrix remodeling: New perspectives as a circulating tool in the diagnosis and prognosis of solid tumors[J]. Cells, 2019, 8(2): 81. DOI: 10.3390/cells8020081.
[17]	ALBRENGUES J, BOURGET I, PONS C, et al. LIF mediates proinvasive activation of stromal fibroblasts in cancer[J]. Cell Rep, 2014, 7(5): 1664-1678. DOI: 10.1016/j.celrep.2014.04.036.
[18]	SHI Y, GAO W, LYTLE NK, et al. Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring[J]. Nature, 2019, 569(7754): 131-135. DOI: 10.1038/s41586-019-1130-6.
[19]	AIELLO NM, KANG Y. Context-dependent EMT programs in cancer metastasis[J]. J Exp Med, 2019, 216(5): 1016-1026. DOI: 10.1084/jem.20181827.
[20]	THOMAS SK, LEE J, BEATTY GL. Paracrine and cell autonomous signalling in pancreatic cancer progression and metastasis[J]. EBioMedicine, 2020, 53: 102662. DOI: 10.1016/j.ebiom.2020.102662.
[21]	XING SN, CHEN W, YU HY. Research status of mesenchymal stem cells on tumorigenesis and development[J]. Clin J Med Offic, 2020, 48(8): 980-982. DOI: 10.16680/j.1671-3826.2020.08.45. 邢思宁, 陈伟, 于卉影. 间充质干细胞对肿瘤发生发展影响研究现状[J]. 临床军医杂志, 2020, 48(8): 980-982. DOI: 10.16680/j.1671-3826.2020.08.45.
[22]	BAPAT AA, HOSTETTER G, von HOFF DD, et al. Perineural invasion and associated pain in pancreatic cancer[J]. Nat Rev Cancer, 2011, 11(10): 695-707. DOI: 10.1038/nrc3131.
[23]	LI X, WANG Z, MA Q, et al. Sonic hedgehog paracrine signaling activates stromal cells to promote perineural invasion in pancreatic cancer[J]. Clin Cancer Res, 2014, 20(16): 4326-4338. DOI: 10.1158/1078-0432.CCR-13-3426.
[24]	BRESSY C, LAC S, NIGRI J, et al. LIF drives neural remodeling in pancreatic cancer and offers a new candidate biomarker[J]. Cancer Res, 2018, 78(4): 909-921. DOI: 10.1158/0008-5472.CAN-15-2790.
[25]	LI C, XU BH. Research progress in clinical application of tumor stem cells[J]. Chin J Oncol Prev Treat, 2021, 13(1): 1-6. DOI: 10.3969/j.issn.1674-5671.2021.01.01. 李聪, 徐兵河. 肿瘤干细胞临床应用研究进展[J]. 中国癌症防治杂志, 2021, 13(1): 1-6. DOI: 10.3969/j.issn.1674-5671.2021.01.01.
[26]	WANG MT, FER N, GALEAS J, et al. Blockade of leukemia inhibitory factor as a therapeutic approach to KRAS driven pancreatic cancer[J]. Nat Commun, 2019, 10(1): 3055. DOI: 10.1038/s41467-019-11044-9.
[27]	CHANG JH, JIANG Y, PILLARISETTY VG. Role of immune cells in pancreatic cancer from bench to clinical application: An updated review[J]. Medicine (Baltimore), 2016, 95(49): e5541. DOI: 10.1097/MD.0000000000005541.
[28]	BLANDO J, SHARMA A, HIGA MG, et al. Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer[J]. Proc Natl Acad Sci U S A, 2019, 116(5): 1692-1697. DOI: 10.1073/pnas.1811067116.
[29]	YU H, YUE X, ZHAO Y, et al. LIF negatively regulates tumour-suppressor p53 through Stat3/ID1/MDM2 in colorectal cancers[J]. Nat Commun, 2014, 5: 5218. DOI: 10.1038/ncomms6218.
[30]	LIU SC, TSANG NM, CHIANG WC, et al. Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance[J]. J Clin Invest, 2013, 123(12): 5269-5283. DOI: 10.1172/JCI63428.
[31]	ARORA GK, GUPTA A, NARAYANAN S, et al. Cachexia-associated adipose loss induced by tumor-secreted leukemia inhibitory factor is counterbalanced by decreased leptin[J]. JCI Insight, 2018, 3(14): e121221. DOI: 10.1172/jci.insight.121221.
[32]	SETO DN, KANDARIAN SC, JACKMAN RW. A key role for leukemia inhibitory factor in C26 cancer cachexia[J]. J Biol Chem, 2015, 290(32): 19976-19986. DOI: 10.1074/jbc.M115.638411.
[33]	KANDARIAN SC, NOSACKA RL, DELITTO AE, et al. Tumour-derived leukaemia inhibitory factor is a major driver of cancer cachexia and morbidity in C26 tumour-bearing mice[J]. J Cachexia Sarcopenia Muscle, 2018, 9(6): 1109-1120. DOI: 10.1002/jcsm.12346.
[34]	HUNTER SA, MCINTOSH BJ, SHI Y, et al. An engineered ligand trap inhibits leukemia inhibitory factor as pancreatic cancer treatment strategy[J]. Commun Biol, 2021, 4(1): 452. DOI: 10.1038/s42003-021-01928-2.
[35]	HURWITZ H, van CUTSEM E, BENDELL J, et al. Ruxolitinib+ capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase Ⅲ studies[J]. Invest New Drugs, 2018, 36(4): 683-695. DOI: 10.1007/s10637-018-0580-2.