title: Side population of a murine mantle cell lymphoma model contains tumour-initiating cells responsible for lymphoma maintenance and dissemination.
abstract: 'Cancer stem cells' or 'tumour initiating cells' in B-cell non-Hodgkin lymphomas have not been demonstrated, although some studies focused on other cancer types suggest that such populations exist and represent tumour cells resistant to therapy and involved in relapse. These cells may also represent a putative neoplastic 'cell of origin' in lymphomas, but there is little substantive data to support this suggestion. Using cell lines derived from a recently established murine IL-14alphax c-Myc double transgenic/mantle cell lymphoma-blastoid variant model, heretofore referred to as DTG cell lines, we identified a subset of cells within the side population (SP) with features of 'tumour-initiating cells'. These features include higher expression of ABCG2 and BCL-2, longer telomere length, greater self-renewal ability and higher in vitro clonogenic and in vivo tumorigenic capacities compared with non-SP. In addition, in vitro viability studies demonstrated that the non-SP lymphoma subpopulation has a limited lifespan in comparison with the SP fraction. Syngenic transplant studies showed that non-SP derived tumours, in comparison to the SP-derived tumours, exhibit greater necrosis/apoptosis and less systemic dissemination capability. In conclusion, our data support the interpretation that the DTG SP fraction contains a cell population highly capable of tumour maintenance and systemic dissemination and lends support to the concept that 'tumour-initiating cells' occur in lymphomas.
authors: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. fvegava@mdanderson.org
authors: Francisco
authors: F
authors: Vega
authors: Yogesh
authors: Y
authors: Davuluri
authors: Jeong Hee
authors: JH
authors: Cho-Vega
authors: Rajesh R
authors: RR
authors: Singh
authors: Shuguang
authors: S
authors: Ma
authors: Rui-Yu
authors: RY
authors: Wang
authors: Asha S
authors: AS
authors: Multani
authors: Elias
authors: E
authors: Drakos
authors: Lan V
authors: LV
authors: Pham
authors: Yen-Chiu Lin
authors: YC
authors: Lee
authors: Long
authors: L
authors: Shen
authors: Julian
authors: J
authors: Ambrus
authors: L Jeffrey
authors: LJ
authors: Medeiros
authors: Richard J
authors: RJ
authors: Ford
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000782:Aneuploidy; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D002999:Clone Cells; D004195:Disease Models, Animal; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016196:S Phase; D013347:Subcellular Fractions / Q000378:metabolism; D016615:Telomere / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D019253:Proto-Oncogene Proteins c-bcl-2; D051997:ADP-ribosyl Cyclase 1