乳腺癌肝转移机制研究进展

doi:10.11904/j.issn.1002-3070.2017.01.010

摘要/Abstract

摘要： 肝脏是乳腺癌常见的转移部位。乳腺癌肝转移的过程包括多个步骤,涉及乳腺癌细胞和肝脏微环境中的多种因素。在本文中,我们综述了与乳腺癌肝转移相关的分子(包括连接蛋白类、蛋白激酶类、miRNAs)、信号转导通路(包括CXCL12-CXCR4轴、Wnt/β-catenin信号通路、AF1q/TCF7/CD44调节轴、层黏连蛋白受体/Akt/ERK信号通路、瘦素/ERK/IL-8信号通路)以及肝脏微环境中的影响因素(包括缺氧诱导因子、肿瘤相关成纤维细胞、脂肪基质干细胞、金属蛋白酶、选择性配体、炎性细胞免疫浸润)。

关键词: 乳腺癌, 肝转移, 微环境

Abstract: Liver is the common metastatic site of breast cancer.The process of liver metastasis consists of multiple steps and involves various factors from breast cancer cells and the liver micro-environment.In this review,we reviewed the molecular(including the connection of proteins,protein kinases,miRNAs),signal transduction pathways(including CXCL12-CXCR4 axis,Wnt/beta-catenin signaling pathway,AF1q/TCF7/CD44 regulatory axis,laminin receptor/Akt/ERK signaling pathway,leptin/ERK/IL-8 signaling pathway)and the influencing factors(including hypoxia inducible factors,tumor-associated fibroblasts,adipose tissue matrix stem cells,metalloproteinases,selective ligands,inflammatory cell infiltration)associated with the liver micro-environment in breast cancer.

Key words: Breast cancer, Liver metastasis, Micro-environment

中图分类号:

R737.9

李博综述, 陈雪松审校. 乳腺癌肝转移机制研究进展[J]. 实用肿瘤学杂志, 2017, 31(1): 48-52.

LI Bo, CHEN Xuesong. Mechanisms involved in liver metastasis of breast cancer[J]. PRACTICAL ONCOLOGY JOURNAL, 2017, 31(1): 48-52.

参考文献

1 Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
2 Ma R,Feng Y,Lin S,et al.Mechanisms involved in breast cancer liver metastasis[J].J Transl Med,2015,15(13):64.
3 Kimbung S,Kovács A,Bendahl PO,et al.Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences[J].Mol Oncol,2014,8(1):119-128.
4 Tabariès S,Annis MG,Hsu BE,et al.Lyn modulates Claudin-2 expression and is a therapeutic target for breast cancer liver metastasis[J].Oncotarget,2015,6(11):9476-9487.
5 Tabariès S,Dupuy F,Dong Z,et al.Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes[J].Mol Cell Biol,2012,32(15):2979-2991.
6 Tabariès S,Dong Z,Annis MG,et al.Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes[J].Oncogene,2011,30(11):1318-1328.
7 Shabo I,Olsson H,Stl O,et al.Breast cancer expression of DAP12 is associated with skeletal and liver metastases and poor survival[J].Clin Breast Cancer,2013,13(5):371-377.
8 Kim HM,Jung WH,Koo JS.Expression of cancer-associated fibroblast related proteins in metastatic breast cancer:an immunohistochemical analysis[J].Transl Med,2015,13(1):1-11.
9 van Roosmalen W,Le Dévédec SE,Golani O,et al.Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant[J].J Clin Invest,2015,125(4):1648-1664.
10 Dupuy F,Tabariès S,Andrzejewski S,et al.PDK1-dependent metabolic reprogramming dictates metastatic potential in breast cancer[J].Cell Metab,2015,22(4):577-589.
11 Endres M,Kneitz S,Orth MF,et al.Regulation of matrix metalloproteinases(MMPs)expression and secretion in MDA-MB-231 breast cancer cells by LIM and SH3 protein 1(LASP1)[J].Oncotarget,2016,7(39):64244-64259.
12 Li X,Liu X,Xu W,et al.c-MYC-regulated miR-23a/24-2/27a cluster promotes mammary carcinoma cell invasion and hepatic metastasis by targeting Sprouty2[J].J Biol Chem,2013,288(25):18121-18133.
13 Salomonnson E,Stacer AC,Ehrlich A,et al.Imaging CXCL12-CXCR4 signaling in ovarian cancer therapy[J].PLoS One,2013,8(1):e51500.
14 Cavallaro S.CXCR4/CXCL12 in non-small-cell lung cancer metastasis to the brain[J].Int J Mol Sci,2013,14(1):1713-1727.
15 Sun Y,Mao X,Fan C,et al.CXCL12-CXCR4 axis promotes the natural selection of breast cancer cell metastasis[J].Tumour Biol,2014,35(8):7765-7773.
16 Bleckmann A,Conradi LC,Menck K,et al.β-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases[J].Clin Exp Metastasis,2016,33(4):309-323.
17 Park J,Schlederer M,Schreiber M,et al.AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis[J].Oncotarget,2015,6(24):20697-20710.
18 Hong H,Zhou T,Fang S,et al.Pigment epithelium-derived factor(PEDF)inhibits breast cancer metastasis by down-regulating fibronectin[J].Breast Cancer Res Treat,2014,148(1):61-72.
19 Cao H,Huang Y,Wang L,et al.Leptin promotes migration and invasion of breast cancer cells by stimulating IL-8 production in M2 macrophages[J].Oncotarget,2016,7(40):65441-65453.
20 Semenza GL.HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations[J].J Clin Invest,2013,123(9):3664-3671.
21 Mi Z,Bhattacharya SD,Kim VM,et al.Osteopontin promotes CCL5-mesenchymal stromal cell-mediated breast cancer metastasis[J].Carcinogenesis,2011,32(4):477-487.
22 Ghattass K,El-Sitt S,Zibara K,et al.The quinoxaline di-N-oxide DCQ blocks breast cancer metastasis in vitro and in vivo by targeting the hypoxia inducible factor-1 pathway[J].Mol Cancer,2014,24(13):12.
23 Madsen CD,Pedersen JT,Venning FA,et al.Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis[J].EMBO Rep,2015,16(10):1394-1408.
24 Strong AL,Ohlstein JF,Biagas BA,et al.Leptin produced by obese adipose stromal/stem cells enhances proliferation and metastasis of estrogen receptor positive breast cancers[J].Breast Cancer Res,2015,19(17):112.
25 Freitas VM,do Amaral JB,Silva TA,et al.Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion[J].Mol Cancer,2013,5(12):2.
26 Choi GC,Li J,Wang Y,et al.The metalloprotease ADAMTS8 displays anti-tumor properties through antagonizing EGFR-MEK-ERK signaling and is silenced in carcinomas by CpG methylation[J].Mol Cancer Res,2014,12(2):228-238.
27 Kelwick R,Wagstaff L,Decock J,et al.Metalloproteinase-dependent and-independent processes contribute to inhibition of breast cancer cell migration,angiogenesis and liver metastasis by a disintegrin and metalloproteina-se with thrombospondinmotifs-15[J].Int J Cancer,2015,136(4):14-26.
28 Woodman N,Pinder SE,Tajadura V,et al.Two E-selectin ligands,BST-2 and LGALS3BP,predict metastasis and poor survival of ER-negative breast cancer[J].Int J Oncol,2016,49(1):265-275.
29 Tabariès S,Ouellet V,Hsu BE,et al.Granulocytic immune infiltrates are essential for the efficient formation of breast cancer liver metastases[J].Breast Cancer Res,2015,27(17):45.

[1]	王晓雅,肖斌,廖扬,唐荣芝,孙朝晖,李林海. CXCR家族蛋白在不同乳腺癌亚型中的表达及临床预后分析[J]. 实用肿瘤学杂志, 2019, 33(3): 206-210.
[2]	李烁,张楠楠,李亮亮,龙志平,尹慧慧,赵亚双,王帆. 外周血白细胞PDE4C基因甲基化及环境因素交互作用与乳腺癌发病的关系[J]. 实用肿瘤学杂志, 2019, 33(3): 233-238.
[3]	李嘉琪,栾瑾微,张,玉,李香兰. 763例三阴性乳腺癌临床病理特征及复发、转移影响因素分析[J]. 实用肿瘤学杂志, 2019, 33(3): 244-249.
[4]	陈艳波, 孔德嘉, 张金锋, 马志刚. 乳腺癌患者CYP2D6基因多态性与他莫昔芬代谢相关性研究[J]. 实用肿瘤学杂志, 2019, 33(2): 110-114.
[5]	孙江宏, 郝明珠, 姜丹, 国飞, 李晓梅. 乳腺炎、良性增生及乳腺癌FFDM鉴别诊断思路[J]. 实用肿瘤学杂志, 2019, 33(2): 139-141.
[6]	马志杰, 王帆, 赵亚双. 乳腺癌化疗患者生存质量及影响因素分析[J]. 实用肿瘤学杂志, 2019, 33(2): 149-154.
[7]	马质莹, 尚乃舰, 蔡妙田, 沈阳, 姜智允. 孕激素及雌激素受体阳性乳腺癌HER-2受体与钼靶影像学特征及临床病理学特征的相关性分析[J]. 实用肿瘤学杂志, 2019, 33(1): 47-51.
[8]	付艳丽, 余杨, 卫玮, 邹晶晶, 孙翔. 高危型人乳头状瘤病毒载量和Th1/Th2不均衡表达预测宫颈癌变进程的研究[J]. 实用肿瘤学杂志, 2018, 32(6): 533-537.
[9]	何煦, 叶尚勉, 董丹丹, 李科. HLA-G在乳腺癌中的表达及意义[J]. 实用肿瘤学杂志, 2018, 32(5): 410-414.
[10]	李悦, 徐可, 韩增祥, 孙敏, 樊国华综述, 张勇审校. 结肠癌中肿瘤相关巨噬细胞的作用及靶向治疗的研究进展[J]. 实用肿瘤学杂志, 2018, 32(5): 450-454.
[11]	韩帮岭, 汪亦民, 薛英威. 中性粒细胞与恶性肿瘤关系的研究进展[J]. 实用肿瘤学杂志, 2018, 32(4): 349-352.
[12]	林荣杰, 尹航, 周云峰. ON123300对ER阳性人乳腺癌MCF-7细胞的影响及机制研究[J]. 实用肿瘤学杂志, 2018, 32(3): 193-197.
[13]	李林(综述), 李志高(审校). 二甲双胍与不同分子亚型乳腺癌的关系[J]. 实用肿瘤学杂志, 2018, 32(3): 267-270.
[14]	吕强, 陈洪生, 李国东, 魏九峰(综述), 刘明(审校). 肿瘤相关成纤维细胞在大肠癌发生发展中的研究进展[J]. 实用肿瘤学杂志, 2018, 32(3): 275-279.
[15]	张培, 曹守波, 于雁. 自噬介导的肿瘤相关巨噬细胞调控机制的研究进展[J]. 实用肿瘤学杂志, 2018, 32(2): 130-134.