Small extracellular vesicles promote the formation of the pre-metastatic niche through multiple mechanisms in colorectal cancer

References

• Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca A Cancer J Clinicians. 2021;71(3):209–249. doi: 10.3322/caac.21660
   PubMed Web of Science ®Google Scholar
• Siegel R-O, Miller K-O, Wagle N-O, et al. Cancer statistics, 2023. Ca A Cancer J Clinicians. 2023;73(1):17–48. doi: 10.3322/caac.21763
   PubMed Web of Science ®Google Scholar
• Valderrama-Treviño AI, Barrera-Mera B, Ceballos-Villalva JC, et al. Hepatic metastasis from colorectal cancer. Euroasian J Hepatogastroenterol. 2017;7(2):166–175. doi: 10.5005/jp-journals-10018-1241
   PubMedGoogle Scholar
• Riihimäki M, Hemminki A, Sundquist J, et al. Patterns of metastasis in colon and rectal cancer. Sci Rep. 2016;6(1):6. doi: 10.1038/srep29765
   PubMedGoogle Scholar
• Psaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nat Rev Cancer. 2009;9(4):285–93. doi: 10.1038/nrc2621
   PubMed Web of Science ®Google Scholar
• Sceneay J, Smyth MJ, Möller A. The pre-metastatic niche: finding common ground. Cancer Metast Rev. 2013;32(3–4):449–64. doi: 10.1007/s10555-013-9420-1
   PubMed Web of Science ®Google Scholar
• Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8(2):98–101.
   PubMed Web of Science ®Google Scholar
• Hart I, Fidler IJ. Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. Cancer Res. 1980;40(7):2281–2287.
   PubMed Web of Science ®Google Scholar
• Liu Y, Cao XT. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30(5):668–81. doi: 10.1016/j.ccell.2016.09.011
   PubMed Web of Science ®Google Scholar
• Kowal J, Tkach M, Théry C. Biogenesis and secretion of exosomes. Curr Opinion Cell Biol. 2014;29:116–25. doi: 10.1016/j.ceb.2014.05.004
   PubMed Web of Science ®Google Scholar
• Johnstone R, Adam M, Hammond J, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987;262(19):9412–9420. doi: 10.1016/S0021-9258(18)48095-7
   PubMed Web of Science ®Google Scholar
• Chang L-O, Chiu HM, Wu MS, et al. The role of small extracellular vesicles in the progression of colorectal cancer and its clinical applications. Int J Mol Sci. 2022;23(3):1379. doi: 10.3390/ijms23031379
   PubMed Web of Science ®Google Scholar
• Meng WR, Hao YY, He CS, et al. Exosome-orchestrated hypoxic tumor microenvironment. Mol Cancer. 2019;18(1):18. doi: 10.1186/s12943-019-0982-6
   PubMedGoogle Scholar
• Mathieu M, Martin-Jaular L, Lavieu G, et al. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9–17. doi: 10.1038/s41556-018-0250-9
   PubMed Web of Science ®Google Scholar
• Greening DW, Gopal SK, Mathias RA, et al. Emerging roles of exosomes during epithelial-mesenchymal transition and cancer progression. Semin Cell Dev Biol. 2015;40:60–71. doi: 10.1016/j.semcdb.2015.02.008
   PubMed Web of Science ®Google Scholar
• Liu XX, Pan B, Sun L, et al. Circulating exosomal miR-27a and miR-130a act as novel diagnostic and prognostic biomarkers of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2018;27(7):746–754. doi: 10.1158/1055-9965.EPI-18-0067
   PubMed Web of Science ®Google Scholar
• Chen MS, Xu R, Rai A, et al. Distinct shed microvesicle and exosome microRNA signatures reveal diagnostic markers for colorectal cancer. PLoS One. 2019;14(1):14. doi: 10.1371/journal.pone.0210003
   Web of Science ®Google Scholar
• Zhou WY, Fong MY, Min YF, et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell. 2014;25(4):501–15. doi: 10.1016/j.ccr.2014.03.007
   PubMed Web of Science ®Google Scholar
• Peinado H, Lavotshkin S, Fau - Lyden D, et al. The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. Semin Cancer Biol. 2011;21(2):139–146. doi: 10.1016/j.semcancer.2011.01.002
   PubMed Web of Science ®Google Scholar
• Feng WL, Dean DC, Hornicek FJ, et al. Exosomes promote pre-metastatic niche formation in ovarian cancer. Mol Cancer. 2019;18(1):18. doi: 10.1186/s12943-019-1049-4
   PubMed Web of Science ®Google Scholar
• Peinado H, Zhang HY, Matei IR, et al. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer. 2017;17(5):302–17. doi: 10.1038/nrc.2017.6
   PubMed Web of Science ®Google Scholar
• Levac D, Colquhoun H, Fau - O’Brien KK, et al. Scoping studies: advancing the methodology. Implement Sci. 2010;20(5):69. doi: 10.1186/1748-5908-5-69
   Google Scholar
• Mariani F, Sena P, Roncucci L. Inflammatory pathways in the early steps of colorectal cancer development. World J Gastroenterol. 2014;20(29):9716–9731. doi: 10.3748/wjg.v20.i29.9716
   PubMed Web of Science ®Google Scholar
• Deng J, Liu Y, Lee H, et al. S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites. Cancer Cell. 2012;21(5):642–54. doi: 10.1016/j.ccr.2012.03.039
   PubMed Web of Science ®Google Scholar
• Yan S-O, Cheng M-O, Duan Q-O, et al. MiR-6803-5p promotes cancer cell proliferation and invasion via PTPRO/NF-κB axis in colorectal cancer. Mediators Inflamm. 2019;20:8128501. doi: 10.1155/2019/8128501
   Google Scholar
• Park SJ, Kim JM, Kim J, et al. Molecular mechanisms of biogenesis of apoptotic exosome-like vesicles and their roles as damage-associated molecular patterns. Procceding of the National Academy of science; USA. 2018;115:E11721–E30 doi: 10.1073/pnas.1811432115.
   Google Scholar
• Ji Q, Zhou LH, Sui H, et al. Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation. Nat Commun. 2020;11(1):11. doi: 10.1038/s41467-020-14869-x
   PubMed Web of Science ®Google Scholar
• Shao Y, Chen T, Zheng X, et al. Colorectal cancer-derived small extracellular vesicles establish an inflammatory premetastatic niche in liver metastasis. Carcinogenesis. 2018;39(11):1368–79. doi: 10.1093/carcin/bgy115
   PubMed Web of Science ®Google Scholar
• Hoshino A, Costa-Silva B, Shen TL, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329–335. doi: 10.1038/nature15756
   PubMed Web of Science ®Google Scholar
• Bodogai M, Moritoh K, Lee-Chang C, et al. Immunosuppressive and prometastatic functions of myeloid-derived suppressive cells rely upon education from tumor-associated B cells. Cancer Res. 2015;75(17):3456–65. doi: 10.1158/0008-5472.CAN-14-3077
   PubMed Web of Science ®Google Scholar
• Zhang WJ, Jiang ZT, Tang D. The value of exosome-derived noncoding RNAs in colorectal cancer proliferation, metastasis, and clinical applications. Clin Transl Oncol. 2022;24(12):2305–18. doi: 10.1007/s12094-022-02908-6
   PubMed Web of Science ®Google Scholar
• Baig MS, Roy A, Rajpoot S, et al. Tumor-derived exosomes in the regulation of macrophage polarization. Inflammation Res. 2020;69(5):435–51. doi: 10.1007/s00011-020-01318-0
   PubMed Web of Science ®Google Scholar
• Xian D, Niu LB, Zeng J, et al. LncRNA KCNQ1OT1 secreted by tumor cell-derived exosomes mediates immune escape in colorectal cancer by regulating PD-L1 ubiquitination MiR-30a-5p/USP22. Front Cell Dev Biol. 2021;9. doi: 10.3389/fcell.2021.653808
   Web of Science ®Google Scholar
• Liu Y, Cao XT. Immunosuppressive cells in tumor immune escape and metastasis. J Mol Med. 2016;94(5):509–522. doi: 10.1007/s00109-015-1376-x
   PubMed Web of Science ®Google Scholar
• Gordon S, Plüddemann A, Estrada FM. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev. 2014;262(1):36–55. doi: 10.1111/imr.12223
   PubMed Web of Science ®Google Scholar
• Mantovani A, Sozzani S, Locati M, et al. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–555. doi: 10.1016/S1471-4906(02)02302-5
   PubMed Web of Science ®Google Scholar
• Wang D, Wang X, Si M, et al. Exosome-encapsulated miRnas contribute to CXCL12/CXCR4-induced liver metastasis of colorectal cancer by enhancing M2 polarization of macrophages. Cancer Lett. 2020;1(474):36–52. doi: 10.1016/j.canlet.2020.01.005
   Google Scholar
• Shinohara H, Kuranaga Y, Kumazaki M, et al. Regulated Polarization of Tumor-Associated Macrophages by miR-145 via Colorectal Cancer–Derived Extracellular Vesicles. The Journal Of Immunology. 2017;199(4):1505–1515. doi: 10.4049/jimmunol.1700167
   PubMed Web of Science ®Google Scholar
• Takano Y, Masuda T, Iinuma H, et al. Circulating exosomal microRNA-203 is associated with metastasis possibly via inducing tumor-associated macrophages in colorectal cancer. Oncotarget. 2017;8(45):78598–613. doi: 10.18632/oncotarget.20009
   PubMedGoogle Scholar
• Zhao S, Mi Y, Guan B, et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol. 2020;13(1):156. doi: 10.1186/s13045-020-00991-2
   PubMed Web of Science ®Google Scholar
• Liang ZX, Liu HS, Wang FW, et al. LncRNA RPPH1 promotes colorectal cancer metastasis by interacting with TUBB3 and by promoting exosomes-mediated macrophage M2 polarization. Cell Death Dis. 2019;10(11):829. 4. doi: 10.1038/s41419-019-2077-0
   PubMed Web of Science ®Google Scholar
• Yang CG, Dou RZ, Wei C, et al. Tumor-derived exosomal microRNA-106b-5p activates EMT-cancer cell and M2-subtype TAM interaction to facilitate CRC metastasis. Mol Ther. 2021;29(6):2088–107. doi: 10.1016/j.ymthe.2021.02.006
   PubMed Web of Science ®Google Scholar
• Rivlin N, Brosh RF, Oren M, et al. Mutations in the p53 tumor suppressor gene: important milestones at the various steps of tumorigenesis. Genes Cancer. 2011;2(4):466–474. doi: 10.1177/1947601911408889
   PubMedGoogle Scholar
• Cooks T, Pateras IS, Jenkins LM, et al. Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246. Nat Commun. 2018;9(1). doi: 10.1038/s41467-018-03224-w
   PubMedGoogle Scholar
• Ursem C, Atreya CE, Van Loon K. Emerging treatment options for BRAF-mutant colorectal cancer. Gastrointest Cancer. 2018;8:13–23. doi: 10.2147/GICTT.S125940
   PubMedGoogle Scholar
• Bhat SA, Ahmad SM, Mumtaz PT, et al. Long non-coding RNAs: mechanism of action and functional utility. Noncoding RNA Res. 2016;12(1):43–50. doi: 10.1016/j.ncrna.2016.11.002
   Google Scholar
• Zhi J, Jia XJ, Yan J, et al. BRAF V600E mutant colorectal cancer cells mediate local immunosuppressive microenvironment through exosomal long noncoding RNAs. World J Gastrointest Oncol. 2021;13(12):2129–2148. doi: 10.4251/wjgo.v13.i12.2129
   PubMed Web of Science ®Google Scholar
• Lu SC, Wei XM, Tao LHP, et al. A novel tRNA-derived fragment tRF-3022b modulates cell apoptosis and M2 macrophage polarization via binding to cytokines in colorectal cancer. J Hematol Oncol. 2022;15(1):15. doi: 10.1186/s13045-022-01388-z
   PubMed Web of Science ®Google Scholar
• Chen J, Li Z, Yue C, et al. Human umbilical cord mesenchymal stem cell-derived exosomes carrying miR-1827 downregulate SUCNR1 to inhibit macrophage M2 polarization and prevent colorectal liver metastasis. LID [doi] - 10.1007/s10495-022-01798-x. Apoptosis. 2023;28(3–4):549–565. doi: 10.1007/s10495-022-01798-x
   PubMed Web of Science ®Google Scholar
• Chen CH, Yao XQ, Xu YH, et al. Dahuang Zhechong Pill suppresses colorectal cancer liver metastasis via ameliorating exosomal CCL2 primed pre-metastatic niche. J Ethnopharmacol. 2019;238:238. doi: 10.1016/j.jep.2019.111878
   Web of Science ®Google Scholar
• Ma YS, Wu TM, Ling CC, et al. M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B. Molecular Therapy-Oncolytics. 2021;20:484–98. doi: 10.1016/j.omto.2021.02.005
   PubMed Web of Science ®Google Scholar
• Masucci MT, Minopoli M, Carriero MV. Tumor associated neutrophils. Their role in Tumorigenesis, metastasis, prognosis and therapy. Front Oncol. 2019;9. doi: 10.3389/fonc.2019.01146
   PubMed Web of Science ®Google Scholar
• Allavena P, Sica A, Garlanda C, et al. The yin-yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev. 2008;222(1):155–161. doi: 10.1111/j.1600-065X.2008.00607.x
   PubMedGoogle Scholar
• Qi MY, Xia Y, Wu YJ, et al. Lin28B-high breast cancer cells promote immune suppression in the lung pre-metastatic niche via exosomes and support cancer progression. Nat Commun. 2022;13(1). doi: 10.1038/s41467-022-28438-x
   Web of Science ®Google Scholar
• Zhang X, Shi H, Yuan X, et al. Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration. Mol Cancer. 2018;17(1):17. doi: 10.1186/s12943-018-0898-6
   PubMedGoogle Scholar
• Shang A, Gu C, Wang W, et al. Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis. Mol Cancer. 2020;19(1):117. doi: 10.1186/s12943-020-01235-0
   PubMed Web of Science ®Google Scholar
• Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer. 2003;3(6):459–65. doi: 10.1038/nrc1097
   PubMed Web of Science ®Google Scholar
• Shang AQ, Gu CZ, Zhou C, et al. Exosomal KRAS mutation promotes the formation of tumor-associated neutrophil extracellular traps and causes deterioration of colorectal cancer by inducing IL-8 expression. Cell Commun Signaling. 2020;18(1):18. doi: 10.1186/s12964-020-0517-1
   PubMed Web of Science ®Google Scholar
• Wang L, Yang J, Huang J, et al. miRNA expression profile in the N2 phenotype neutrophils of colorectal cancer and screen of putative key miRnas. Cancer Manage Res. 2020;12:5491–5503. doi: 10.2147/CMAR.S251427
   PubMed Web of Science ®Google Scholar
• Sakaguchi S, Miyara M, Fau - Costantino CM, et al. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010;10(7):490–500. doi: 10.1038/nri2785
   PubMed Web of Science ®Google Scholar
• Nishikawa H, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Cell Res. 2017;27(1):109–118. doi: 10.1038/cr.2016.151
   PubMed Web of Science ®Google Scholar
• Wang M, Qin ZY, Wan JJ, et al. Tumor-derived exosomes drive pre-metastatic niche formation in lung via modulating CCL1 fibroblast and CCR8 treg cell interactions. Cancer Immunol Immunother. 2022;71(11):2717–2730. doi: 10.1007/s00262-022-03196-3
   PubMed Web of Science ®Google Scholar
• Huang MY, Huang X, Huang N. Exosomal circGSE1 promotes immune escape of hepatocellular carcinoma by inducing the expansion of regulatory T cells. Cancer Sci. 2022;113(6):1968–83. doi: 10.1111/cas.15365
   PubMed Web of Science ®Google Scholar
• Chen YY, Li ZY, Liang JF, et al. CircRNA has_circ_0069313 induced OSCC immunity escape by miR-325-3p-Foxp3 axes in both OSCC cells and treg cells. Aging-Us. 2022;14(10):4376–89. doi: 10.18632/aging.204068
   Web of Science ®Google Scholar
• Yamada N, Kuranaga Y, Kumazaki M, et al. Colorectal cancer cell-derived extracellular vesicles induce phenotypic alteration of T cells into tumor-growth supporting cells with transforming growth factor-β1-mediated suppression. Oncotarget. 2016;7(9):27033–27043. 10. doi: 10.18632/oncotarget.7041
   PubMedGoogle Scholar
• Ning T, Li JL, He Y, et al. Exosomal miR-208b related with oxaliplatin resistance promotes treg expansion in colorectal cancer. Mol Ther. 2021;29(9):2723–36. doi: 10.1016/j.ymthe.2021.04.028
   PubMed Web of Science ®Google Scholar
• Milette S, Sicklick JK, Lowy AM, et al. Molecular pathways: targeting the microenvironment of liver metastases. Clin Cancer Res. 2017;23(21):6390–9. doi: 10.1158/1078-0432.CCR-15-1636
   PubMed Web of Science ®Google Scholar
• Meng XJ, Huang ZQ, Teng FF, et al. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 2015;41(10):868–76. doi: 10.1016/j.ctrv.2015.11.001
   PubMed Web of Science ®Google Scholar
• Chen G, Huang AC, Zhang W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018;560(7718):382–386. doi: 10.1038/s41586-018-0392-8
   PubMed Web of Science ®Google Scholar
• Padoan A, Plebani M, Basso D. Inflammation and pancreatic cancer: focus on metabolism, cytokines, and immunity. Int J Mol Sci. 2019;20(3):676. 5. doi: 10.3390/ijms20030676
   PubMed Web of Science ®Google Scholar
• Li R, Wen A, Lin J-O. Pro-inflammatory cytokines in the formation of the pre-metastatic niche. Cancers (Basel). 2020;12(12):3752. doi: 10.3390/cancers12123752
   PubMed Web of Science ®Google Scholar
• Wang YG, Ding YX, Guo NZ, et al. Mdscs: key criminals of tumor pre-metastatic niche formation. Front Immunol. 2019;10:10. doi: 10.3389/fimmu.2019.00172
   PubMed Web of Science ®Google Scholar
• Jiang MM, Zhang WW, Zhang R, et al. Cancer exosome-derived miR-9 and miR-181a promote the development of early-stage MDSCs via interfering with SOCS3 and PIAS3 respectively in breast cancer. Oncogene. 2020;39(24):4681–94. doi: 10.1038/s41388-020-1322-4
   PubMed Web of Science ®Google Scholar
• Guo XF, Qiu W, Liu QL, et al. Immunosuppressive effects of hypoxia-induced glioma exosomes through myeloid-derived suppressor cells via the miR-10a/and miR-21/Pathways. Oncogene. 2018;37(31):4239–4259. doi: 10.1038/s41388-018-0261-9
   PubMed Web of Science ®Google Scholar
• Guo XF, Qiu W, Wang J, et al. Glioma exosomes mediate the expansion and function of myeloid-derived suppressor cells through microRNA-29a/ Hbp1 and microRNA-92a/ Prkar1a pathways. Intl J Cancer. 2019;144(12):3111–3126. doi: 10.1002/ijc.32052
   PubMed Web of Science ®Google Scholar
• Eisenblaetter M, Flores-Borja F, Lee JJ, et al. Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment. Theranostics. 2017;7(9):2392–401. doi: 10.7150/thno.17138
   PubMed Web of Science ®Google Scholar
• Wang YG, Yin K, Tian J, et al. Granulocytic myeloid-derived suppressor cells promote the stemness of colorectal cancer cells through exosomal S100A9. Adv Sci. 2019;6(18):6. doi: 10.1002/advs.201901278
   Web of Science ®Google Scholar
• Ham B, Wang N, D’Costa Z, et al. TNF receptor-2 facilitates an immunosuppressive microenvironment in the liver to promote the colonization and growth of hepatic metastases. Cancer Res. 2015;75(24):5235–47. doi: 10.1158/0008-5472.CAN-14-3173
   PubMed Web of Science ®Google Scholar
• Tian XY, Shen H, Li ZY, et al. Tumor-derived exosomes, myeloid-derived suppressor cells, and tumor microenvironment. J Hematol Oncol. 2019;12(1):12. doi: 10.1186/s13045-019-0772-z
   PubMed Web of Science ®Google Scholar
• Weis SM, Cheresh DA. Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med. 2011;17(1):1359–1370. doi: 10.1038/nm.2537
   PubMedGoogle Scholar
• Tang YF, Zong SQ, Zeng HL, et al. MicroRNAs and angiogenesis: a new era for the management of colorectal cancer. Cancer Cell Int. 2021;21(1):21. doi: 10.1186/s12935-021-01920-0
   PubMed Web of Science ®Google Scholar
• Yamada N-O, Heishima K, Akao Y, et al. Extracellular vesicles containing MicroRNA-92a-3p facilitate partial endothelial-mesenchymal transition and angiogenesis in endothelial cells. Int J Mol Sci. 2019;20(18):4406. doi: 10.3390/ijms20184406
   PubMed Web of Science ®Google Scholar
• Zeng ZC, Li YL, Pan YJ, et al. Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis. Nat Commun. 2018;9(1). doi: 10.1038/s41467-018-07810-w
   Google Scholar
• Yin H, Yu SS, Xie YY, et al. Cancer-associated fibroblasts-derived exosomes upregulate microRNA-135b-5p to promote colorectal cancer cell growth and angiogenesis by inhibiting thioredoxin-interacting protein. Cell Signal. 2021;84:84. doi: 10.1016/j.cellsig.2021.110029
   Web of Science ®Google Scholar
• Hu HY, Yu CH, Zhang HH, et al. Exosomal miR-1229 derived from colorectal cancer cells promotes angiogenesis by targeting HIPK2. Int j biol macromol. 2019;132:470–7. doi: 10.1016/j.ijbiomac.2019.03.221
   PubMed Web of Science ®Google Scholar
• Huang Z, Fau - Feng Y, Feng Y. Exosomes derived from hypoxic colorectal cancer cells promote angiogenesis through Wnt4-induced β-catenin signaling in endothelial cells. Oncol Res. 2017;25(5):651–661. doi: 10.3727/096504016X14752792816791
   PubMed Web of Science ®Google Scholar
• He QL, Ye AH, WBA Y, et al. Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1. Cell Death Dis. 2021;12(6):12. doi: 10.1038/s41419-021-03803-8
   PubMed Web of Science ®Google Scholar
• Shang AQ, Wang X, Gu CZ, et al. Exosomal miR-183-5p promotes angiogenesis in colorectal cancer by regulation of FOXO1. Aging-Us. 2020;12(9):8352–71. doi: 10.18632/aging.103145
   Web of Science ®Google Scholar
• Wang FW, Cao CH, Han K, et al. APC-activated long noncoding RNA inhibits colorectal carcinoma pathogenesis through reduction of exosome production. J Clin Invest. 2019;129(2):727–43. 1. doi: 10.1172/JCI122478
   PubMed Web of Science ®Google Scholar
• Chen C, Liu Y, Liu L, et al. Exosomal circTUBGCP4 promotes vascular endothelial cell tipping and colorectal cancer metastasis by activating Akt signaling pathway. J Exp Clin Cancer Res. 2023;42(1):42. doi: 10.1186/s13046-023-02619-y
   PubMed Web of Science ®Google Scholar
• Jiang K, Chen HY, Fang YM, et al. Exosomal ANGPTL1 attenuates colorectal cancer liver metastasis by regulating kupffer cell secretion pattern and impeding MMP9 induced vascular leakiness. J Exp Clin Cancer Res. 2021;40(1):40. doi: 10.1186/s13046-020-01816-3
   PubMed Web of Science ®Google Scholar
• He Y, Rajantie I, Ilmonen M, et al. Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis. Cancer Res. 2004;64(11):3737–3740. 1. doi: 10.1158/0008-5472.CAN-04-0088
   PubMed Web of Science ®Google Scholar
• Achen MG, Stacker SA. Molecular control of lymphatic metastasis. Annals Of The New York Academy Of Sciences. 2008;1131(1):1131:225–34. doi: 10.1196/annals.1413.020
   PubMedGoogle Scholar
• Wakisaka N, Hasegawa Y, Yoshimoto S, et al. Primary tumor-secreted lymphangiogenic factors induce pre-metastatic lymphvascular niche formation at sentinel lymph nodes in oral squamous cell carcinoma. PloS One. 2015;10(12):10. doi: 10.1371/journal.pone.0144056
   Web of Science ®Google Scholar
• Sun B, Zhou YM, Fang YT, et al. Colorectal cancer exosomes induce lymphatic network remodeling in lymph nodes. Intl J Cancer. 2019;145(6):1648–1659. doi: 10.1002/ijc.32196
   PubMed Web of Science ®Google Scholar
• Zhang L, Yuan JT, Ocansey DKW, et al. Exosomes derived from human umbilical cord mesenchymal stem cells regulate lymphangiogenesis via the miR-302d-3p/VEGFR3/AKT axis to ameliorate inflammatory bowel disease. Int Immunopharmacol. 2022;110:110. doi: 10.1016/j.intimp.2022.109066
   Web of Science ®Google Scholar
• Wang X, Ding XL, Nan LJ, et al. Investigation of the roles of exosomes in colorectal cancer liver metastasis. Oncol Rep. 2015;33(5):2445–53. doi: 10.3892/or.2015.3843
   PubMed Web of Science ®Google Scholar
• Sun H, Meng QT, Shi CY, et al. Hypoxia-Inducible Exosomes Facilitate Liver-Tropic Premetastatic Niche in Colorectal Cancer. Hepatology. 2021;74(5):2633–51. doi: 10.1002/hep.32009
   PubMed Web of Science ®Google Scholar
• Mannavola F, Salerno T, Passarelli A, et al. Revisiting the role of exosomes in colorectal cancer: where are we Now? Front Oncol. 2019;19(9):521. doi: 10.3389/fonc.2019.00521
   Google Scholar
• Guo YX, Ji X, Liu JB, et al. Effects of exosomes on pre-metastatic niche formation in tumors. Mol Cancer. 2019;18(1):18. doi: 10.1186/s12943-019-0995-1
   PubMed Web of Science ®Google Scholar
• Scherz-Shouval R, Santagata S, Mendillo ML, et al. The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy. Cell. 2014;158(3):564–78. doi: 10.1016/j.cell.2014.05.045
   PubMed Web of Science ®Google Scholar
• Wu ZM, Wei D, Gao WC, et al. TPO-Induced metabolic reprogramming drives liver metastasis of colorectal cancer CD110+Tumor-initiating cells. Cell Stem Cell. 2015;17(1):47–59. doi: 10.1016/j.stem.2015.05.016
   PubMed Web of Science ®Google Scholar
• Yamamura Y, Asai N, Enomoto A, et al. Akt–girdin signaling in cancer-associated fibroblasts contributes to tumor progression. Cancer Research. 2015;75(5):813–823. doi: 10.1158/0008-5472.CAN-14-1317
   PubMed Web of Science ®Google Scholar
• Rai A, Greening DW, Chen MS, et al. Exosomes derived from human primary and metastatic colorectal cancer cells contribute to functional heterogeneity of activated fibroblasts by reprogramming their proteome. Proteomics. 2019;19(8). doi: 10.1002/pmic.201800148
   Web of Science ®Google Scholar
• Rai A, Greening DW, Xu R, et al. Exosomes derived from the human primary colorectal cancer cell line SW480 orchestrate fibroblast-led cancer invasion. Proteomics. 2020;20(14):20. doi: 10.1002/pmic.202000016
   Web of Science ®Google Scholar
• Zhang C, Wang XY, Zhang P, et al. Cancer-derived exosomal HSPC111 promotes colorectal cancer liver metastasis by reprogramming lipid metabolism in cancer-associated fibroblasts. Cell Death Dis. 2022;13(1). doi: 10.1038/s41419-022-04506-4
   Web of Science ®Google Scholar
• Nairon KG, DePalma TJ, Zent JM, et al. Tumor cell-conditioned media drives collagen remodeling via fibroblast and pericyte activation in an in vitro premetastatic niche model. iScience. 2022;25(7):104645. doi: 10.1016/j.isci.2022.104645
   PubMed Web of Science ®Google Scholar
• Weyemi U, Redon CE, Choudhuri R, et al. The histone variant H2A.X is a regulator of the epithelial–mesenchymal transition. Nat Commun. 2016;7(1):10711. doi: 10.1038/ncomms10711
   PubMedGoogle Scholar
• Cui TX, Kryczek I, Zhao L, et al. Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity. 2013;39(3):611–621. doi: 10.1016/j.immuni.2013.08.025
   PubMed Web of Science ®Google Scholar
• Ombrato L, Nolan E, Kurelac I, et al. Metastatic-niche labelling reveals parenchymal cells with stem features. Nature. 2019;572(7771):603–608. doi: 10.1038/s41586-019-1487-6
   PubMed Web of Science ®Google Scholar
• Tang Q-O, Chen J, Di Z, et al. TM4SF1 promotes EMT and cancer stemness via the Wnt/β-catenin/SOX2 pathway in colorectal cancer. J Exper Cli Can Res CR. 2020;39(1):232. doi: 10.1186/s13046-020-01690-z
   PubMed Web of Science ®Google Scholar
• Pradella D, Naro C, Sette C, et al. EMT and stemness: flexible processes tuned by alternative splicing in development and cancer progression. Mol Cancer. 2017;16(1):8. doi: 10.1186/s12943-016-0579-2
   PubMedGoogle Scholar
• Bai J, Zhang X, Shi D, et al. Exosomal miR-128-3p promotes epithelial-to-mesenchymal transition in colorectal cancer cells by targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 signaling. Front Cell Dev Biol. 2021;9:568738. doi: 10.3389/fcell.2021.568738
   PubMed Web of Science ®Google Scholar
• Miao Z, Zhao X, Liu X. Exosomal circCOL1A2 from cancer cells accelerates colorectal cancer progression via regulating miR-665/LASP1 signal axis. Eur J Pharmacol. 2023;950:175722. doi: 10.1016/j.ejphar.2023.175722
   PubMed Web of Science ®Google Scholar
• Fang X, Xu Y, Li K, et al. Exosomal lncRNA PCAT1 promotes tumor circulating cell-mediated colorectal cancer liver metastasis by regulating the activity of the miR-329-3p/Netrin-1-CD146 complex. J Immunol Res. 2022;2022:9916228. doi: 10.1155/2022/9916228
   PubMed Web of Science ®Google Scholar
• Sun X, Lin F, Sun W, et al. Exosome-transmitted miRNA-335-5p promotes colorectal cancer invasion and metastasis by facilitating EMT via targeting RASA1. Mol Ther Nucleic Acids. 2021;164–174. doi: 10.1016/j.omtn.2021.02.022
   PubMedGoogle Scholar
• Cheung AHK, Chow C, To KF. Latest development of liquid biopsy. J. Thorac. Dis. 2018;10(S14):S1645–S51. doi: 10.21037/jtd.2018.04.68
   PubMedGoogle Scholar
• Sheridan C. Exosome cancer diagnostic reaches market. Nat Biotechnol. 2016;34(4):358–359. doi: 10.1038/nbt0416-359
   Web of Science ®Google Scholar
• Cheng N, Du D, Wang XX, et al. Recent advances in biosensors for detecting cancer-derived exosomes. Trends Biotechnol. 2019;37(11):1236–54. doi: 10.1016/j.tibtech.2019.04.008
   PubMed Web of Science ®Google Scholar
• Xu JS, Liao KL, Zhou WM. Exosomes regulate the transformation of cancer cells in cancer stem cell homeostasis. Stem Cells Int. 2018;2018:1–16. doi: 10.1155/2018/4837370
   Web of Science ®Google Scholar
• Hu JL, Wang W, Lan XL, et al. Cafs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer. Mol Cancer. 2019;18(1):18. doi: 10.1186/s12943-019-1019-x
   PubMedGoogle Scholar
• Bhome R, Goh RW, Bullock MD, et al. Exosomal microRnas derived from colorectal cancer-associated fibroblasts: role in driving cancer progression. Aging-Us. 2017;9(12):2666–94. doi: 10.18632/aging.101355
   Web of Science ®Google Scholar
• Danova M, Comolli G, Manzoni M, et al. Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: a critical evaluation. Mol Clin Oncol. 2016;4(6):909–17. doi: 10.3892/mco.2016.823
   PubMedGoogle Scholar
• Avallone A, Piccirillo MC, Aloj L, et al. A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (optimization of BEvacizumab scheduLing within chemotherapy scheme). BMC Cancer. 2016;16(1). doi: 10.1186/s12885-016-2102-y
   PubMedGoogle Scholar
• Liu CY, Su CQ. Design strategies and application progress of therapeutic exosomes. Theranostics. 2019;9(4):1015–28. doi: 10.7150/thno.30853
   PubMed Web of Science ®Google Scholar
• Abak A, Abhari A, Rahimzadeh S. Exosomes in cancer: small vesicular transporters for cancer progression and metastasis, biomarkers in cancer therapeutics. PeerJ. 2018;6:6. doi: 10.7717/peerj.4763
   Web of Science ®Google Scholar
• Kalimuthu S, Gangadaran P, Rajendran RL, et al. A new approach for loading anticancer drugs into mesenchymal stem cell-derived exosome mimetics for cancer therapy. Front Pharmacol. 2018;9. doi: 10.3389/fphar.2018.01116
   Web of Science ®Google Scholar