3 外泌体介导肝癌和其他细胞间的通讯

肝癌细胞、脂肪细胞、成纤维细胞、免疫细胞等细胞组成了一个复杂的肝癌微环境，外泌体作为细胞通讯的介质，负责着这些细胞间的信息传递。体外实验发现，用HepG2-exo 处理可以改变脂肪细胞的转录组，并激活其NF-κB 信号通路，上调相关炎症因子的表达。而当用HepG2-exo 处理过的脂肪细胞与肝癌细胞共培养时，可以促进肝癌细胞的增殖和转移[22]。对于免疫细胞，肝癌外泌体可以将14-3-3ζ蛋白递送至肿瘤浸润性T淋巴细胞（TIL），从而抑制其抗肿瘤功能[23]。另有研究表明，肿瘤外泌体可以通过递送miR-1247-3p 诱导癌相关的成纤维细胞活化[24]；或递送原癌蛋白和RNA 至肝细胞，增强其运动能力来促进HCC 转移时的肝实质突出活动[25]，从而促进肝癌的转移。值得关注的是，非肿瘤细胞来源的外泌体也可以起到抑制肿瘤的作用，如肥大细胞[26]、树突细胞（DC）[27]和脂肪间充质干细胞（AMSC）[28]等。这也提示未来基于外泌体的干细胞疗法和免疫疗法治疗肿瘤的可能性。

4 结语

自外泌体受到关注以来，学者们针对其进行了大量研究，其中外泌体与肿瘤的关系更是关注的热点（PubMed 检索显示相关文章约占外泌体文章总数的40%）。本文仅整理并阐述了外泌体在肝癌微环境中的通讯中的作用，其作用方式主要包括：①外泌体将相关活性物质（ncRNA、蛋白等）由高增殖性/高侵袭性/高耐药的肿瘤细胞递送至低增殖性/低侵袭性/低耐药的肿瘤细胞或正常细胞，从而促进后者的恶性增殖、转移和多药耐药；②肿瘤外泌体作用于临近或远端的非肿瘤细胞（如免疫细胞、血管内皮细胞、脂肪细胞和成纤维细胞等），改变后者的生命活动，再正向或负向调节肿瘤细胞，实现对肿瘤的促进或抑制；③肿瘤患者血清外泌体可以在一定程度上反映原位肿瘤的特征，可作为肿瘤诊断与预后的理想材料。理解并应用这些机制，在未来外泌体的临床转化上有着非凡的意义。

[1]Torre L A, Bray F, Siegel R L, et cancer statistics, 2012[J].CA Cancer J Clin, 2015,65(2):87-108.

[2]Chen W Q, Zheng R S, Baade P D, et sta?tistics in China, 2015[J].CA Cancer J Clin, 2016,66(2):115-132.

[3]Berretta M, Cavaliere C, Alessandrini L, et al.Serum and tissue markers in hepatocellular carcinoma and cholangiocarcinoma: clinical and prognostic implications[J].Oncotarget, 2017,8(8):-.

[4]Heitzer E, Ulz P, Geigl J tumor DNA as a liquid biopsy for cancer[J].Clin Chem, 2015,61(1):112-123.

[5]Wan Z, Gao X, Dong Y, et cell-cell communication in tumor progression[J].Am J Cancer Res, 2018,8(9):1661-1673.

[6]Guo W, Gao Y, Li N, et : new players in cancer[J].Oncol Rep, 2017,38(2):665-675.

[7]Yang H, Fu H, Xu W, et non-coding RNAs a promising cancer biomarker[J].Clin Chem Lab Med, 2016,54(12):1871-1879.

[8]Wang Z, Chen J Q, Liu J L, et in tu?mor microenvironment novel transporters and biomark?ers[J].J Transl Med, 2016,14(1):297.

[9]Batrakova E V, Kim M S.Using exosomes, naturallyequipped nanocarriers, for drug delivery[J].J Control Release, 2015,219:396-405.

[10]Hui L L, Chen Y.Tumor microenvironment: sanctuary of the devil[J].Cancer Lett, 2015,368(1):7-13.

[11]Chen L, Guo P, He Y, et exosomes elicit HCC progression and recurrence by epithelialmesenchymal transition through MAPK/ERK signalling pathway[J].Cell Death Dis, 2018,9(5):513.

[12]Xiao D, Barry S, Kmetz D, et cell-de?rived exosomes promote epithelial-mesenchymal transi?tion in primarymelanocytes through paracrine/autocrine signaling in the tumor microenvironment[J].Can?cer Lett, 2016,376(2):318-327.

[13]Xue X, Wang X, Zhao Y, et miR-93 promotes proliferation and invasion in hepatocellular carcinoma by directly inhibiting TIMP2/TP53INP1/CD?KN1A[J].Biochem Biophys Res Commun, 2018,502(4):515-521.

[14]Li B, Mao R, Liu C, et FAL1 promotes cell proliferation and migration by acting as a CeR?NA of miR-1236 in hepatocellular carcinoma cells[J].Life Sci, 2018,197:122-129.

[15]Qu Z, Wu J, Wu J, et derived from HCC cells induce sorafenib resistance in hepatocellu?lar carcinoma both in vivo and in vitro[J].J Exp Clin Cancer Res, 2016,35(1):159.

[16]Fu X, Liu M, Qu S, et microRNA-32-5p induces multidrug resistance in hepatocellular carci?noma via the PI3K/Akt pathway[J].J Exp Clin Can?cer Res, 2018,37(1):52.

[17]Takahashi K, Yan I K, Kogure T, et vesicle- mediated transfer of long non- coding RNA ROR modulates chemosensitivity in human hepatocellu?lar cancer[J].FEBS Open Bio, 2014,4:458-467.

[18]Takahashi K, Yan I K, Wood J, et of extracellular vesicle long noncoding RNA(linc- VLD?LR) in tumor cell responses to chemotherapy[J].Mol Cancer Res, 2014,12(10):1377-1387.

[19]Yukawa H, Suzuki K, Aoki K, et of angio?genesis of human umbilical vein endothelial cells by uptake of exosomes secreted from hepatocellular carci?noma cells[J].Sci Rep, 2018,8(1):6765.

文章来源：《化工设计通讯》 网址: http://www.hgsjtxzz.cn/qikandaodu/2021/0718/827.html