摘要
癌症是一种慢性疾病,涉及肿瘤和宿主基质细胞的多种成分。目前,肿瘤微环境(TME)中存在的各种因素与肿瘤细胞以及位于TME内的免疫细胞之间的复杂关系仍知之甚少。在 TME 内,这些因素和免疫细胞的串扰从根本上决定了肿瘤对治疗的反应以及肿瘤最终如何被破坏、保持休眠或发展和转移。此外,在 TME 中,癌症相关成纤维细胞 (CAF)、细胞外基质 (ECM)、缺氧诱导因子 (HIF) 之间的相互串扰增强了癌症干细胞 (CSC) 的增殖能力。 CSC 是位于肿瘤块内的细胞亚群,具有自我更新、分化和修复 DNA 损伤的能力。这些特性使 CSC 对各种治疗产生耐药性,例如放疗 (RT)。 RT 是一种常见且经常治愈的局部癌症治疗方法,它通过细胞毒性作用介导肿瘤消除。此外,释放到 TME 中的细胞因子和生长因子参与了肿瘤放射抗性的激活和不同免疫细胞的诱导,从而改变了局部免疫反应。在这篇综述中,我们讨论了 TME 在 CSCs 对 RT 的抵抗中的关键作用。
关键词: 放疗、肿瘤干细胞、肿瘤微环境、肿瘤相关成纤维细胞、细胞外基质、缺氧诱导因子
图形摘要
[http://dx.doi.org/10.1016/j.phrs.2020.104745] [PMID: 32145401]
[http://dx.doi.org/10.1016/j.intimp.2020.106663] [PMID: 32521494]
[http://dx.doi.org/10.1016/j.intimp.2019.105847] [PMID: 31466051]
[http://dx.doi.org/10.1016/j.lfs.2020.117570] [PMID: 32205088]
[http://dx.doi.org/10.1002/jcb.27681] [PMID: 30321449]
[http://dx.doi.org/10.1007/s12032-020-01447-w] [PMID: 33394200]
[http://dx.doi.org/10.1002/cbin.11506] [PMID: 33236822]
[http://dx.doi.org/10.1016/j.lfs.2020.118110] [PMID: 32698074]
[http://dx.doi.org/10.1371/journal.pone.0031467] [PMID: 22328933]
[http://dx.doi.org/10.1038/s41571-019-0293-2] [PMID: 31792354]
[http://dx.doi.org/10.1158/0008-5472.CAN-18-2952] [PMID: 31088838]
[http://dx.doi.org/10.1016/j.ijrobp.2018.09.003] [PMID: 30213750]
[http://dx.doi.org/10.29252/ijrr.19.1.175]
[http://dx.doi.org/10.1038/s41571-018-0007-1] [PMID: 29651130]
[http://dx.doi.org/10.1002/stem.2596] [PMID: 28207184]
[http://dx.doi.org/10.1016/j.ccr.2012.02.022] [PMID: 22439926]
[http://dx.doi.org/10.3389/fmolb.2019.00160] [PMID: 32118030]
[http://dx.doi.org/10.1007/s10585-019-09966-1] [PMID: 30972526]
[http://dx.doi.org/10.1016/S0167-8140(04)80031-8] [PMID: 15971325]
[http://dx.doi.org/10.1080/09553000400001006] [PMID: 15586882]
[http://dx.doi.org/10.1038/nrc3958] [PMID: 26105538]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0703] [PMID: 16061655]
[http://dx.doi.org/10.3389/fnmol.2019.00131] [PMID: 31191243]
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0524] [PMID: 29217764]
[http://dx.doi.org/10.1002/mc.23205] [PMID: 32363633]
[http://dx.doi.org/10.3389/fmolb.2019.00070] [PMID: 31475157]
[http://dx.doi.org/10.1667/RR13583.1] [PMID: 24785588]
[http://dx.doi.org/10.1038/cddis.2017.180] [PMID: 28518141]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6390] [PMID: 18519702]
[PMID: 14617784]
[http://dx.doi.org/10.4161/cbt.3.1.570] [PMID: 14726672]
[http://dx.doi.org/10.1186/s12885-019-5768-0] [PMID: 31200666]
[http://dx.doi.org/10.1016/j.suronc.2012.06.001] [PMID: 22749313]
[http://dx.doi.org/10.1093/jnci/djv017] [PMID: 25710962]
[http://dx.doi.org/10.18632/oncotarget.3535] [PMID: 25843954]
[http://dx.doi.org/10.1159/000430138] [PMID: 26021266]
[http://dx.doi.org/10.1186/s12885-015-1086-3] [PMID: 25881239]
[http://dx.doi.org/10.2174/1574888X15999200831160710] [PMID: 32867660]
[http://dx.doi.org/10.1155/2017/5619472] [PMID: 5619472]
[http://dx.doi.org/10.3390/cancers11040434] [PMID: 30934773]
[http://dx.doi.org/10.18632/oncotarget.23607] [PMID: 30279970]
[http://dx.doi.org/10.1155/2017/3714190] [PMID: 3714190]
[http://dx.doi.org/10.1016/j.ebiom.2017.03.004] [PMID: 28274806]
[http://dx.doi.org/10.1186/s13046-019-1110-6] [PMID: 30841909]
[http://dx.doi.org/10.1101/gad.279737.116] [PMID: 27151975]
[http://dx.doi.org/10.1371/journal.pgen.1006244] [PMID: 27541266]
[http://dx.doi.org/10.1371/journal.pone.0015313] [PMID: 21249190]
[http://dx.doi.org/10.1007/s12079-021-00648-w] [PMID: 34611852]
[http://dx.doi.org/10.1016/j.intimp.2021.107895] [PMID: 34171623]
[http://dx.doi.org/10.1111/bcpt.13648] [PMID: 34473898]
[http://dx.doi.org/10.1172/JCI120481] [PMID: 29863500]
[http://dx.doi.org/10.1021/acs.nanolett.6b04150] [PMID: 28027646]
[http://dx.doi.org/10.1002/jcp.27740] [PMID: 30417375]
[http://dx.doi.org/10.15252/embr.201439246] [PMID: 25381661]
[http://dx.doi.org/10.1038/nrclinonc.2016.60] [PMID: 27141887]
[http://dx.doi.org/10.1038/bjc.2016.152] [PMID: 27219018]
[http://dx.doi.org/10.1038/s41418-019-0292-y] [PMID: 30728463]
[PMID: 947858]
[http://dx.doi.org/10.1038/ncb3041] [PMID: 25266422]
[http://dx.doi.org/10.1073/pnas.1017360108] [PMID: 21518860]
[http://dx.doi.org/10.1073/pnas.1520032112] [PMID: 26512116]
[http://dx.doi.org/10.1158/1078-0432.CCR-09-2730] [PMID: 20103663]
[http://dx.doi.org/10.1182/blood-2017-10-810176] [PMID: 29724896]
[http://dx.doi.org/10.12703/P6-13] [PMID: 24669294]
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[http://dx.doi.org/10.1186/s12885-018-4441-3] [PMID: 29751789]
[http://dx.doi.org/10.1016/j.it.2004.09.015] [PMID: 15530839]
[PMID: 20830235]
[http://dx.doi.org/10.1084/jem.20180818] [PMID: 30470719]
[http://dx.doi.org/10.1186/s13287-018-1102-z] [PMID: 30635041]
[http://dx.doi.org/10.1002/stem.118] [PMID: 19544427]
[http://dx.doi.org/10.1371/journal.pone.0097256] [PMID: 24826993]
[http://dx.doi.org/10.1101/cshperspect.a026781] [PMID: 28213438]
[http://dx.doi.org/10.1038/s41568-019-0238-1] [PMID: 31980749]
[http://dx.doi.org/10.3892/ol.2021.12674] [PMID: 33841574]
[http://dx.doi.org/10.1084/jem.20140692] [PMID: 25071162]
[http://dx.doi.org/10.1038/nrc2714] [PMID: 19693095]
[http://dx.doi.org/10.1038/nrc.2016.73] [PMID: 27550820]
[http://dx.doi.org/10.2174/092986708784049667] [PMID: 18393855]
[http://dx.doi.org/10.18632/oncotarget.15119] [PMID: 28186964]
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0023] [PMID: 23824740]
[http://dx.doi.org/10.1182/blood.V108.11.2048.2048]
[http://dx.doi.org/10.1016/j.yexcr.2020.111956] [PMID: 32169425]
[http://dx.doi.org/10.18632/oncotarget.14752] [PMID: 28121625]
[http://dx.doi.org/10.1371/journal.pone.0125625] [PMID: 25938772]
[http://dx.doi.org/10.1038/s41389-017-0011-9] [PMID: 29362402]
[http://dx.doi.org/10.1186/s12943-019-0994-2] [PMID: 30927908]
[http://dx.doi.org/10.3389/fimmu.2019.01835] [PMID: 31428105]
[http://dx.doi.org/10.4161/cc.7.9.5804] [PMID: 18418042]
[http://dx.doi.org/10.1186/1465-9921-12-76] [PMID: 21658209]
[http://dx.doi.org/10.4161/cc.7.13.6203] [PMID: 18604161]
[http://dx.doi.org/10.1073/pnas.1013805107] [PMID: 21041659]
[http://dx.doi.org/10.1016/j.matbio.2012.11.016] [PMID: 23262216]
[http://dx.doi.org/10.1016/j.cell.2005.02.034] [PMID: 15882617]
[http://dx.doi.org/10.1007/82_2010_73]
[http://dx.doi.org/10.1259/0007-1285-26-312-638] [PMID: 13106296]
[PMID: 13708070]
[http://dx.doi.org/10.1201/b15450]
[http://dx.doi.org/10.1158/0008-5472.CAN-16-1887] [PMID: 28209613]
[http://dx.doi.org/10.1038/oncsis.2015.35] [PMID: 26619402]
[http://dx.doi.org/10.3109/09553002.2014.916841] [PMID: 24844374]
[http://dx.doi.org/10.1186/s13058-018-0944-8] [PMID: 29510720]
[http://dx.doi.org/10.1038/ncomms6203] [PMID: 25351418]
[http://dx.doi.org/10.1089/cbr.2008.0492] [PMID: 18986217]
[http://dx.doi.org/10.3389/fcell.2017.00101] [PMID: 29270405]
[http://dx.doi.org/10.1615/CritRevOncog.v18.i1-2.70] [PMID: 23237555]
[http://dx.doi.org/10.1016/j.semcdb.2009.10.010] [PMID: 19896548]
[http://dx.doi.org/10.1097/01.moh.0000219664.26528.da] [PMID: 16567962]
[http://dx.doi.org/10.1089/lrb.2007.1014] [PMID: 18370914]
[http://dx.doi.org/10.1016/j.febslet.2009.07.011] [PMID: 19596003]
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a003231] [PMID: 12204104]
[http://dx.doi.org/10.1182/blood-2008-02-133751] [PMID: 19060246]
[http://dx.doi.org/10.1007/s00262-016-1879-5] [PMID: 27497816]
[PMID: 28560067]
[http://dx.doi.org/10.1016/j.molcel.2010.09.022] [PMID: 20965423]
[http://dx.doi.org/10.1016/j.cell.2007.04.019] [PMID: 17482542]
[http://dx.doi.org/10.1186/1475-2867-13-119] [PMID: 24305593]
[http://dx.doi.org/10.1093/jrr/rrw012] [PMID: 26983985]
[http://dx.doi.org/10.1074/jbc.M800102200] [PMID: 18281291]
[http://dx.doi.org/10.1124/mol.106.027029] [PMID: 16887934]
[http://dx.doi.org/10.1017/S1462399409001173] [PMID: 19709449]
[http://dx.doi.org/10.1016/S1535-6108(04)00115-1] [PMID: 15144951]
[http://dx.doi.org/10.1038/sj.onc.1210556] [PMID: 17563752]
[http://dx.doi.org/10.1038/ncomms1786] [PMID: 22510688]
[http://dx.doi.org/10.1186/s13014-018-1153-4] [PMID: 29304828]
[http://dx.doi.org/10.20517/2394-4722.2020.49]
[http://dx.doi.org/10.1093/abbs/gmt141] [PMID: 24395300]
[http://dx.doi.org/10.5306/wjco.v5.i5.1068] [PMID: 25493243]
[http://dx.doi.org/10.1186/s13046-020-1535-y] [PMID: 31928527]
[http://dx.doi.org/10.1080/15384047.2015.1030545] [PMID: 25891797]
[http://dx.doi.org/10.1002/path.5405] [PMID: 32100288]
[http://dx.doi.org/10.1016/j.cell.2009.02.006] [PMID: 19239885]
[http://dx.doi.org/10.1016/j.cell.2018.03.068]
[PMID: 29115513]
[http://dx.doi.org/10.1016/j.biopha.2017.01.049] [PMID: 28122299]
[http://dx.doi.org/10.1038/s41418-019-0381-y] [PMID: 31320749]
[http://dx.doi.org/10.1016/j.yexcr.2017.06.016] [PMID: 28689810]