Yuan Dandan, Chen Liang, Li Mingxing, Xia Hongwei, Zhang Yuchen, Chen Tie, Xia Rui, Tang Qiulin, Gao Fabao, Mo Xianming, Liu Ming, Bi Feng
Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, 610041, China.
J Cancer Res Clin Oncol. 2015 Apr;141(4):647-60. doi: 10.1007/s00432-014-1814-0. Epub 2014 Oct 18.
Circulating tumor cells (CTCs) have been proved to be responsible for tumor metastasis and resistant to anticancer therapies. This study aims to isolate and characterize circulating tumor cells from human gastric cancer patients, and investigate characteristic differences between gastric CTCs and gastric cancer cell lines.
We analyzed 31 cases of gastric cancer patients using anti-CD45 antibody-conjugated magnetic microbeads negative separation, combined with fluorescence activated cell sorter CD44 positive screening. Abilities of tumor formation, metastasis, invasion, migration, irradiation and drug sensitivity of CTCs and gastric cancer cell lines were detected and compared.
Of all the 31 patients, CD44(+)/CD45(-)CTCs were isolated in 14 patients, of which 3 cases were stage IIA, 2 cases stage IIB, 2 cases stage IIIC and 7 cases stage IV. The malignant behavior was demonstrated by both clonogenetic assay and tumor xenograft in nude mice. Compared with human gastric cancer cell lines, the migration and invasion abilities of CTCs increased to 3.21-12.6-fold and 2.3-6.7-fold, respectively (all p values <0.05). In addition, the metastatic potential of CTCs is much higher in vivo than that of the control. Furthermore, CTCs were found to be relatively sensitive to FU, cisplatin and paclitaxel, but relatively resistant to irradiation, oxaliplatin, cetuximab and trastuzumab.
CD44(+)/CD45(-) gastric CTCs were isolated and found to exhibit stronger malignant behavior when compared with human gastric cancer cell lines. Furthermore, CTCs cultured in vitro have potential implications in drug sensitivity screening for the future anticancer treatments.
循环肿瘤细胞（CTCs）已被证明与肿瘤转移及抗癌治疗耐药有关。本研究旨在从人胃癌患者中分离并鉴定循环肿瘤细胞，并研究胃癌CTCs与胃癌细胞系之间的特征差异。
我们采用抗CD45抗体偶联磁微珠阴性分选，结合荧光激活细胞分选仪CD44阳性筛选，分析了31例胃癌患者。检测并比较了CTCs和胃癌细胞系的肿瘤形成、转移、侵袭、迁移、辐射及药物敏感性能力。
31例患者中，14例分离出CD44(+)/CD45(-)CTCs，其中IIA期3例，IIB期2例，IIIC期2例，IV期7例。克隆形成试验和裸鼠肿瘤异种移植均证实了其恶性行为。与人类胃癌细胞系相比，CTCs的迁移和侵袭能力分别提高到3.21 - 12.6倍和2.3 - 6.7倍（所有p值<0.05）。此外，CTCs在体内的转移潜能远高于对照组。此外，发现CTCs对氟尿嘧啶、顺铂和紫杉醇相对敏感，但对辐射、奥沙利铂、西妥昔单抗和曲妥珠单抗相对耐药。
分离出CD44(+)/CD45(-)胃CTCs，发现其与人类胃癌细胞系相比表现出更强的恶性行为。此外，体外培养的CTCs对未来抗癌治疗的药物敏感性筛选具有潜在意义。
