<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Cell Cycle and Proliferative Activity of Human Colon Cancer Initiating Cells"^^ . "In human colon cancer only a small subfraction of all tumor cells is able to rebuild the\r\ntumor in immunodeficient mice. It has been hypothesized that the proliferative activity\r\nof these tumor initiating cells (TIC) may differ from the bulk of the tumor cells and that\r\nmitotic quiescence of TIC may contribute to chemotherapy resistance or relapse after\r\ntreatment. By genetic marking, it has previously been shown that a variable proportion\r\nof all human TIC contributed to tumor xenograft formation only late after serial\r\ntransplantation suggesting that these delayed contributing TIC indeed might have been\r\nquiescent in primary recipient mice.\r\nIn order to investigate the cell cycle and proliferative activity of human colon TIC in\r\nvitro and in vivo, human colon cancer patient samples were dissociated and cultured\r\nunder serum free conditions favoring the outgrowth of tumor spheres enriched for TIC.\r\nThe CFSE label-retaining assay was used to analyze the proliferative activity of human\r\ncolon TIC in vitro. It allowed discrimination of fast (F), slow (S) and rarely dividing (R)\r\ncell fractions suggesting that a rarely dividing population of human colon TIC might\r\nexist in vivo as well. Cell surface markers previously associated with tumor initiating\r\npotential (CD133, CD44, EpCAM and CD166) were equally expressed in all\r\nproliferative subfractions. A limiting dilution assay confirmed the self-renewal potential\r\nof spheroid cells. Furthermore, it revealed that the frequency of sphere forming cells\r\n(SFC) was similar in the fast, slow and rarely dividing fraction within individual sphere\r\nlines, demonstrating that the vast majority of all SFC were rapidly cycling in vitro. To\r\nassess the in vivo tumor initiating potential and self-renewal ability, equal cell numbers\r\nof sorted R, S and F cells were transplanted into immunodeficient mice. All sorted cell\r\nfractions of three patients formed tumors, irrespective of their proliferative kinetics in\r\nvitro. Moreover, the majority of cells within serially transplanted tumors originating\r\nfrom CFSE+ fractions lost fluorescence intensity indicating that they actively cycled\r\nafter transplantation. Hoechst/Pyronin-staining of dissociated sphere cells allowed\r\ninvestigation of their cell cycle status. Equal numbers of G1-, S/G2/M- and G0-cells were\r\ntransplanted under the kidney capsule of immunodeficient mice. Each cell fraction\r\ncomprised self-renewing, human colon TIC as shown by a serial transplantation assay.\r\nIn order to investigate the proliferative activity of human colon TIC within an\r\nestablished tumor in vivo, intra-tumoral cell divisions were tracked using a genetic high\r\nresolution label-retaining assay. A tetracycline-regulated H2B-GFP expression system\r\nwas implemented into spheroid cells by lentiviral transduction prior to transplantation.\r\nH2B-GFP-expression was suppressed after establishment of the tumor\r\nmicroenvironment. Further cell divisions dilute the GFP-label and thereby enable\r\nSummary II\r\nanalysis of the cell’s proliferative activity. FACS analysis of formed tumors revealed\r\nfast, slow and rarely dividing cell fractions in vivo. All cell fractions harbored selfrenewing,\r\nhuman colon TIC as shown by serial transplantation. Interestingly, only\r\nquiescent TIC showed a polyclonal contribution to tumor formation in mice. A\r\nproportion of quiescent TIC might have been activated to proliferate upon\r\nchemotherapeutic treatment.\r\nThis study demonstrates that human colon cancer harbours tumor initiating cells with\r\ndiffering cell cycle status and proliferative activity. Self-renewing colon TIC were\r\npresent in all cell cycle phases demonstrating that the tumor initiating potential is not\r\nrestricted to a dormant cell cycle status. A rarely dividing population of human colon\r\nTIC derived from different patient samples exists in vitro and in vivo. However, the\r\nmajority of colon TIC rapidly divided in sphere cultures as well as in vivo. Colon TIC\r\nwere found to be enriched in the quiescent population and were recruited to tumor\r\nformation upon chemotherapeutic treatment. Our results provide basis for a better\r\nunderstanding of quiescence and proliferation of human colon TIC. This will hopefully\r\nlead to the development of innovative treatment strategies directed against colon cancer\r\ninitiating cells."^^ . "2014" . . . . . . . "Eva-Maria"^^ . "Hartinger"^^ . "Eva-Maria Hartinger"^^ . . . . . . "Cell Cycle and Proliferative Activity of Human Colon Cancer Initiating Cells (PDF)"^^ . . . "DA_EMH_final.pdf"^^ . . . "Cell Cycle and Proliferative Activity of Human Colon Cancer Initiating Cells (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Cell Cycle and Proliferative Activity of Human Colon Cancer Initiating Cells (Other)"^^ . . . . . . "Cell Cycle and Proliferative Activity of Human Colon Cancer Initiating Cells (Other)"^^ . . . . . . "Cell Cycle and Proliferative Activity of Human Colon Cancer Initiating Cells (Other)"^^ . . . . . . "Cell Cycle and Proliferative Activity of Human Colon Cancer Initiating Cells (Other)"^^ . . . . . "HTML Summary of #15535 \n\nCell Cycle and Proliferative Activity of Human Colon Cancer Initiating Cells\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . .