title: Highly enriched CD133(+)CD44(+) stem-like cells with CD133(+)CD44(high) metastatic subset in HCT116 colon cancer cells.
abstract: Stem-like cancer cells (SLCCs) are distinct cellular subpopulation in colon cancer that is essential for tumor maintenance. Previous studies indicated that SLCCs accounted for only a minor subset in a given cancer model. However, we found that SLCCs frequency varied among a panel of colon cancer cell lines, with HCT116 cells composed mainly of SLCCs, as demonstrated by colonosphere forming capability and CD133 expression. Indeed, flow cytometric analysis revealed more than 60% HCT116 cells co-expressed the putative SLCCs markers CD133 and CD44. Compared with non-CD133(+)CD44(+) cells, FACS sorted CD133(+)CD44(+) cells were undifferentiated, endowed with extensive self-renewal and epithelial lineage differentiation capacity in vitro. CD133(+)CD44(+) exhibited enhanced tumorigeneicity in NOD/SCID mice. One thousand CD133(+)CD44(+) cells initiated xenograft tumors efficiently (3/6) while 1 × 10(5) non-CD133(+)CD44(+) cells could only form palpable nodule with much slower growth rate (1/6). More interestingly, long-term cultured self-renewing CD133(+)CD44(+) cells enriched CD133(+)CD44(high) subset, which expressed epithelial to mesenchymal transition marker, were more invasive in vitro and responsible solely for liver metastasis in vivo. In conclusion, these data demonstrated for the first time that CD133(+)CD44(+) SLCCs were highly enriched in HCT116 cells and that metastatic SLCCs resided exclusively in a CD133(+)CD44(high) subpopulation.
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ke-li
authors.initials: KL
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.forename: Heng
authors.initials: H
authors.lastname: Jiang
authors.forename: Jian-fang
authors.initials: JF
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Pei
authors.forename: Fang-wei
authors.initials: FW
authors.lastname: Xie
authors.forename: Hou-jie
authors.initials: HJ
authors.lastname: Liang
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D012333:RNA, Messenger