Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients

被引:144
作者
Chen, Tie [2 ]
Yang, Kun [1 ]
Yu, Jianhua [2 ]
Meng, Wentong [2 ]
Yuan, Dandan [3 ]
Bi, Feng [3 ]
Liu, Fang [2 ]
Liu, Jie [1 ]
Dai, Bing [1 ]
Chen, Xinzu [1 ]
Wang, Fang [1 ]
Zeng, Fan [2 ]
Xu, Hong [2 ]
Hu, Jiankun [1 ]
Mo, Xianming [2 ]
机构
[1] Sichuan Univ, Dept Gastrointestinal Surg, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, Lab Stem Cell Biol, Chengdu 610041, Sichuan, Peoples R China
[3] Sichuan Univ, State Key Lab Biotherapy, W China Hosp, W China Med Sch, Chengdu 610041, Sichuan, Peoples R China
关键词
cancer stem cells; gastric adenocarcinoma; CD44; CD54; circulating tumor cells; METASTATIC BREAST-CANCER; DISEASE PROGRESSION; SURVIVAL; EXPRESSION; CD44;
D O I
10.1038/cr.2011.109
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Gastric cancer is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. To date, there is a lack of efficient therapeutic protocols for gastric cancer. Recent studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation, invasion, metastasis, and resistance to anticancer therapies. Thus, therapies that target gastric CSCs are attractive. However, CSCs in human gastric adenocarcinoma (GAC) have not been described. Here, we identify CSCs in tumor tissues and peripheral blood from GAC patients. CSCs of human GAC (GCSCs) that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers, generated tumors that highly resemble the original human tumors when injected into immunodeficient mice, differentiated into gastric epithelial cells in vitro, and self-renewed in vivo and in vitro. Our findings suggest that effective therapeutic protocols must target GCSCs. The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor metastasis, and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.
引用
收藏
页码:248 / 258
页数:11
相关论文
共 29 条
[1]   Prospective identification of tumorigenic breast cancer cells [J].
Al-Hajj, M ;
Wicha, MS ;
Benito-Hernandez, A ;
Morrison, SJ ;
Clarke, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988
[2]   Age-Specific Trends in Incidence of Noncardia Gastric Cancer in US Adults [J].
Anderson, William F. ;
Camargo, M. Constanza ;
Fraumeni, Joseph F., Jr. ;
Correa, Pelayo ;
Rosenberg, Philip S. ;
Rabkin, Charles S. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2010, 303 (17) :1723-1728
[3]   Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro [J].
Barker, Nick ;
Huch, Meritxell ;
Kujala, Pekka ;
van de Wetering, Marc ;
Snippert, Hugo J. ;
van Es, Johan H. ;
Sato, Toshiro ;
Stange, Daniel E. ;
Begthel, Harry ;
van den Born, Maaike ;
Danenberg, Esther ;
van den Brink, Stieneke ;
Korving, Jeroen ;
Abo, Arie ;
Peters, Peter J. ;
Wright, Nick ;
Poulsom, Richard ;
Clevers, Hans .
CELL STEM CELL, 2010, 6 (01) :25-36
[4]   Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].
Bonnet, D ;
Dick, JE .
NATURE MEDICINE, 1997, 3 (07) :730-737
[5]   Gastric cancer: Preoperative local staging with 3D multi-detector row CT - Correlation with surgical and histopathologic results [J].
Chen, Chiao-Yun ;
Hsu, Jui-Sheng ;
Wu, Deng-Chyang ;
Kang, Wan-Yi ;
Hsieh, Jan-Sing ;
Jaw, Twei-Shiun ;
Wu, Ming-Tsang ;
Liu, Gin-Chung .
RADIOLOGY, 2007, 242 (02) :472-482
[6]   Pathology of Gastric Intestinal Metaplasia: Clinical Implications [J].
Correa, Pelayo ;
Piazuelo, M. Blanca ;
Wilson, Keith T. .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2010, 105 (03) :493-498
[7]   Circulating tumor cells, disease progression, and survival in metastatic breast cancer [J].
Cristofanilli, M ;
Budd, GT ;
Ellis, MJ ;
Stopeck, A ;
Matera, J ;
Miller, MC ;
Reuben, JM ;
Doyle, GV ;
Allard, WJ ;
Terstappen, LWMM ;
Hayes, DF .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (08) :781-791
[8]   Circulating tumor cells, disease progression, and survival in metastatic breast cancer [J].
Cristofanilli, Massimo .
SEMINARS IN ONCOLOGY, 2006, 33 (03) :S9-S14
[9]   CANCER STEM CELLS Here, there, everywhere? [J].
Eaves, Connie J. .
NATURE, 2008, 456 (7222) :581-582
[10]  
House Michael G, 2008, Adv Surg, V42, P151, DOI 10.1016/j.yasu.2008.04.003