title: CXCR4 positive cells from Lewis lung carcinoma cell line have cancer metastatic stem cell characteristics.
abstract: There is increasing evidence that cancer stem cells contribute to the initiation and propagation of many tumor. Therefore, to find out and identify the metastatic tumor stem-like cells in Lewis lung cancer cell line (LLC), the expression of CXCR4 was measured in LLC by flow cytometry and observed by laser scanning confocal microscope (LSCM). After the CXCR4(+) LLC cell was isolated from LLC by magnetic cell sorting, its properties were evaluated by their tumorigenic and metastatic potentials. CXCR4(+) cells were counted for 0.18% of the total number of LLC, and immunofluorescent staining cells were identified by LSCM. CXCR4(+) LLC suspension cultured in a serum-free medium, cell spheres expressed a high level of Sca-1. The chemotherapy sensitivity to cisplatin of CXCR4(+) LLC was lower than that of CXCR4(-) LLC. The expression of ABCG2 and IGF1R mRNA in CXCR4(+) LLC was higher than that in CXCR4(-) LLC (P < 0.01). Most of CXCR4(+) LLC cells were close to vascular endothelial cells, aberrant vasculature around it was forming. The expression of VEGF and MMP9 mRNA in CXCR4(+) LLC was higher than that in CXCR4(-) LLC (P < 0.05), the microvessel density (MVD) of CXCR4(+) subsets growing were higher than that of CXCR4(-) subsets growing tumor tissue (P < 0.01). The tumor size, volume, and metastatic foci in the lungs of CXCR4(+) LLC was significantly higher than that in CXCR4(-) LLC (P < 0.001). Similarly, elevated expression of MMP9 and VEGF was also positively associated with CXCR4(+) LLC. Our results demonstrated that CXCR4(+) cells from Lewis lung carcinoma cell line exhibit cancer metastatic stem cell characteristics.
authors.affiliation: Cancer Institute of the People's Liberation Army, Xinqiao Hospital, Third Military Medical University, 29 Xinqiao Main Street, Chongqing 400037, People's Republic of China.
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: Nian
authors.forename: Fang-Lin
authors.initials: FL
authors.lastname: Chen
authors.forename: Xu-Jun
authors.initials: XJ
authors.lastname: Ao
authors.forename: Zheng-Tang
authors.initials: ZT
authors.lastname: Chen
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D055786:Gene Knockout Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D015703:Antigens, CD; D000970:Antineoplastic Agents; C514936:CXCR4 protein, mouse; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D017526:Receptor, IGF Type 1; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D002945:Cisplatin