目前，随着富集和捕获循环肿瘤细胞(CTCs)技术的发展，研究转移起始时刻的癌细胞特征成为可能。因此，CTCs将有望成为癌症患者进行实时检测治疗效果及预后评价的有效指标。然而，由于血液中CTCs数量有限，并且转移过程中癌细胞表型不断改变，使得CTCs利用受到限制。目前已发展出多种不同方法在体内外扩展CTCs，旨在研究具有干细胞特性的功能性转移起始CTCs的特征，并以此得到新的诊疗工具。本综述叙述了已有的CTC体外培养和CTC来源的异种移植，以识别由CTCs起始的转移相关的分子机制，还讨论了EMT与CTC特征的关系，以及这些特征如何与肿瘤微环境中的其他因素相互作用，导致了肿瘤细胞在远处器官的扩散和增殖。

[1] LAMBERT A W,PATTABIRAMAN D R,WEINBERG R A.Emerging biological principles of metastasis[J].Cell,2017,168(4):670-691.
[2] BOBEK V,KOLOSTOVA K,LIBERKO M.Essentials of circulating tumor cells for clinical research and practice[J].Crit Rev Oncol Hematol，2013，88(2):338-356.
[3] PANTEL K,KANG Y.Tumor cell dissemination:emerging biological insights from animal models and cancer patients[J].Cancer Cell，2013，23(5):573-581.
[4] RUPP B,BALL H,WUCHU F,et al.Circulating tumor cells in precision medicine:challenges and opportunities[J].Trends Pharmacol Sci，2022，43(5)：378-391.
[5] PANTEL K,ALIX-PANABIERES C.Circulating tumour cells in cancer patients:challenges and perspectives[J].Trends Mol Med，2010，16(9):398-406.
[6] KARACHALIOU N,ROSELL R.Lung cancer:using ctDNA to track EGFR and KRAS mutations in advanced-stage disease[J].Nat Rev Clin Oncol，2016，13(7):401-402.
[7] ANDREE K C,DALUM G V,TERSTAPPEN L W M M.Challenges in circulating tumor cell detection by the cell search system[J].Mol Oncol，2016，10(3):395-407.
[8] YATES L R,DESMEDT C.Translational genomics:practical applications of the genomic revolution in breast cancer[J].Clin Cancer Res，2017，23(11):2630-2639.
[9] RISBRIDGER G P,TOIVANEN R,TAYLOR R A.Preclinical models of prostate cancer:patient-derived xenografts,organoids,and other explant models[J].Cold Spring Harb Perspect Med，2018，8(8):a030536.
[10] LANGHANS S A.Three-dimensional in vitro cell culture models in drug discovery and drug repositioning[J].Front Pharmacol，2018，23(9):6.
[11] PANTEL K,ALIX-PANABIERES A.Liquid biopsy and minimal residual disease-latest advances and implications for cure[J].Nat Rev Clin Oncol，2019，16(7):409-424.
[12] ZHANG L X,RIDGWAY L D,WETZEL M D,et al.The identification and characterization of breast cancer CTCs competent for brain metastasis[J].Sci Transl Med，2013，5(189):189er5.
[13] GINESTIER C,HUR M H,DONTU G,et al.ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome[J].Cell Stem Cell，2007,1(5):555-567.
[14] MCGOWAN P M,SIMEDREA C,RIBOT E F,et al.Notch1 inhibition alters the CD44hi/CD24lo population and reduces the formation of brain metastases from breast cancer[J].Mol Cancer Res，2011，9(7):834-844.
[15] VISHNOI M,PEDDIBHOTLA S,WEI Y,et al.The isolation and characterization of CTC subsets related to breast cancer dormancy[J].Sci Rep，2015，5:17533.
[16] ACETO N,BARDIA A,MIYAMOTO D T,et al.Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis[J].Cell，2014，158(5):1110-1122.
[17] KHOO B L,LEE S C,KUMAR P et al.Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy[J].Oncotarge，2015，6(17):15578-15593.
[18] ZHANG Z,SHIRATSUCHI H,LIN J,et al.Expansion of CTCs from early stage lung cancer patients using a microfluidic co-culture mode[J].Oncotarget，2014，5(23):12383-12397.
[19] QUE Z J,LUO B,ZHOU ZH Y,et al.Establishment and characterization of a patient-derived circulating lung tumor cell line in vitro and in vivo[J].Cancer Cell Int，2019，19:21.
[20] HAMILTON G,HOCHMAIR M,RATH B,et al.Small cell lung cancer:circulating tumor cells of extended stage patients express a mesenchymal-epithelial transition phenotype[J].Cell Adh Migr，2016，10(4):360-367.
[21] HUSSAIN S H,HUERTAS C S,MITCHELL A,et al.Biosensors for circulating tumor cells(CTCs)-biomarker detection in lung and prostate cancer:trends and prospects[J].Biosens Bioelectron，2022，197:113770.
[22] LI W,LIU J B,HOU L K,et al.Liquid biopsy in lung cancer:significance in diagnostics,prediction,and treatment monitoring[J].Mol Cancer，2022，21(1):25.
[23] 姜磊，黄婧，许莹莹，等.循环肿瘤细胞评估甲状腺髓样癌预后的应用价值初步研究[J].东南大学学报(医学版)，2022，41(2)：255-259.
[24] BRINCKERHOFF C E.Cancer stem cells(CSCs) in melanoma:there's smoke,but is there fire?[J].J Cell Physio，2017，232(10):2674-2678.
[25] MANI S A,GUO W J,LIAO M J,et al.The epithelial-mesenchymal transition generates cells with properties of stem cells[J].Cell，2008，133(4):704-715.
[26] HORIMOTO Y,TOKUDA E,MURAKAMI F,et al.Analysis of circulating tumour cell and the epithelial mesenchymal transition(EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer:a pilot study[J].J Transl Med，2018，16(1):287.
[27] CHENG Y H,CHEN Y C,LIN E,et al.Hydro-seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells[J].Nat Commun，2019，10(1):2163.
[28] XU J S,LIAO K L,YANG X,et al.Using single-cell sequencing technology to detect circulating tumor cells in solid tumors[J].Mol Cancer，2021，20(1):104.
[29] YU M,BARDIA A,ACETO N,et al.Cancer therapy.Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility[J].Science，2014，345(6193):216-220.
[30] KATS-UGURLU G,ROODINK I,WEIJERT M D,et al.Circulating tumour tissue fragments in patients with pulmonary metastasis of clear cell renal cell carcinoma[J].J Pathol，2009，219(3):287-293.
[31] CAYREFOURCQ L,MAZARD T,JOOSSE S,et al.Establishment and characterization of a cell line from human circulating colon cancer cells[J].Cancer Res，2015，75(5):892-901.
[32] GKOUNTELA S,CASTRO-GINER F,SZCZERBA B M,et al.Circulating tumor cell clustering shapes DNA methylation to enable metastasis seeding[J].Cell，2019，176(1-2):98-112.
[33] KAUSHIK V,YAKISICH J S,AZAD N,et al.Anti-tumor effects of cardiac glycosides on human lung cancer cells and lung tumorspheres[J].J Cell Physiol，2017，232(9):2497-2507.
[34] LIN D F,SHEN L,LUO M,et al.Circulating tumor cells:biology and clinical significance[J].Signal Transduct Target Ther，2021，6(1):404.
[35] LAMBERT A W,WEINBERG R A.Linking EMT programmes to normal and neoplastic epithelial stem cells[J].Nat Rev Cancer，2021，21(5):325-338.
[36] DONGRE A,WEINBERG R A.New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer[J].Nat Rev Mol Cell Biol，2019，20(2):69-84.
[37] RZHEVSKIY A,KAPITANNIKOVA A,MALININA P,et al.Emerging role of circulating tumor cells in immunotherapy[J].Theranostics，2021，11(16):8057-8075.
[38] YU W,HURLEY J,ROBERTS D,et al.Exosome-based liquid biopsies in cancer:opportunities and challenges[J].Ann Oncol，2021，32(4):466-477.
[39] SZCZERBA B M,CASTRO-CINER F,VETTER M,et al.Neutrophils escort circulating tumour cells to enable cell cycle progression[J].Nature，2019，566(7745):553-557.
[40] 单海琳，邵清，苏瑛，等.乳腺癌术前外周血循环肿瘤细胞计数的临床应用价值研究[J].东南大学学报(医学版)，2018，37(2)：272-276.
[41] HE S T,YU S C H,WEI J L,et al.New horizons in the identification of circulating tumor cells(CTCs):an emerging paradigm shift in cytosensors[J].Biosens Bioelectron，2022，203:114043.
[42] YANG J N,CHENG S S,ZHANG N,et al.Liquid biopsy for ovarian cancer using circulating tumor cells:recent advances on the path to precision medicine[J].Biochim Biophys Acta Rev Cancer，2022，1877(1):188660.