CD44+ CD133+ population exhibits cancer stem cell-like characteristics in human gallbladder carcinoma.
Cancer stem cells (CSCs)/tumor-initiating cells have been defined as a subset of tumor cells responsible for initiating and sustaining tumor development. Emerging evidence strongly supports the existence of CSCs in various solid tumors, but they have not yet been identified in human gallbladder carcinomas (GBC). In this study, we identified CSCs in primary GBC and in the cell line GBC-SD using the cell surface markers CD44 and CD133. The percentages of CD44+CD133+ cells were 1.76-3.05% in primary tumors and 40.29% in GBC-SD cells. These cells showed stem cell properties, including self-renewal, differentiation potential, and high tumorigenicity. In vitro culture experiments revealed that CD44+CD133+ GBC cells possessed a higher spheroid-colony forming ability in serum-free media than other subpopulations. When injected into nonobese diabetic/severe combined immunodeficient mice, these cells formed new tumors and generated CD44+CD133+, CD44-, and CD133- progeny. CD44+CD133+ cells also showed a high degree of chemoresistance, possibly due to upregulation of the breast cancer resistance protein (ABCG2) and the transcription factor Gli1 in these highly tumorigenic cells. These results suggest that the CD44+CD133+ population exhibited CSC-like characteristics and may thus provide a novel approach to the diagnosis and treatment of GBC.
Department of Biliary-pancreatic Surgery, Tongji Hospital, Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chengjian
C
Shi
Rui
R
Tian
Min
M
Wang
Xin
X
Wang
Jianxin
J
Jiang
Zhifa
Z
Zhang
Xu
X
Li
Zheng
Z
He
Weiqiang
W
Gong
Renyi
R
Qin
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D005706:Gallbladder Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D010455:Peptides / Q000276:immunology; D018874:Spheroids, Cellular; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation; D000071676:Zinc Finger Protein GLI1; D000093542:Gemcitabine
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D015513:Oncogene Proteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine