Origin pro 8 shirley
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(E) Representative images of DTCs from CMV TKO and CGRP TKO mice. Immunofluorescence staining for Nfib on FACS-isolated GFP positive DTCs from the pleural cavity and cancer cells from liver metastases from CMV TKO and CGRP TKO mice. The colors of the largest primary tumors, disseminated tumors cells (DTCs), and metastases are shown. Summary of results from 4 CMV TKO Motley mice and 4 CGRP TKO Motley mice. All The DTCs of this mouse have the same color (CFP positive and YFP positive). Representative FACS analysis on disseminated tumor cells (DTCs) from a CGRP TKO Motley mouse. Primary tumors existed in multiple colors, while all metastases from the same mouse had the same color, suggesting that these metastases are clonally related to one primary tumor.
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Representative images of tumors and metastases from TKO Motley mice with CGRP-Cre-initiated SCLC.
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Not every mouse developed metastatic disease at the time of analysis even though each mouse in this analysis had several large primary tumors (7–11 months after initiation). Occurrence of metastasis in CMV TKO and CGRP TKO mice. ©2018 American Association for Cancer Research.Ī. 1216 This article is highlighted in the In This Issue feature, p. See related commentary by Pozo et al., p. Understanding intertumoral heterogeneity in SCLC, and across cancer types, may illuminate mechanisms of tumor progression and uncover how the cell type of origin affects tumor evolution. Significance: We show that SCLC can arise from different cell types of origin, which profoundly influences the eventual genetic and epigenetic changes that enable metastatic progression. Our findings underscore the importance of the identity of cell type of origin in influencing tumor evolution and metastatic mechanisms. Underlying the difference between the two programs was the cell type of origin of the tumors, with NFIB-independent metastases arising from mature neuroendocrine cells. Gene-expression and chromatin accessibility analyses identify distinct mechanisms as well as markers predictive of metastatic progression in both groups. In one model, tumors gain metastatic ability through amplification of the transcription factor NFIB and a widespread increase in chromatin accessibility, whereas in the other model, tumors become metastatic in the absence of NFIB-driven chromatin alterations. Here, using genetically defined mouse models of small cell lung cancer (SCLC), we uncovered distinct metastatic programs attributable to the cell type of origin. extent to which early events shape tumor evolution is largely uncharacterized, even though a better understanding of these early events may help identify key vulnerabilities in advanced tumors. 16 Cancer Biology Program, Stanford University, Stanford, California.15 Department of Computer Science, Stanford University, Stanford, California.14 Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia.13 Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.12 Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases, University of Cologne, Cologne, Germany.11 Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany.10 Comprehensive Cancer Center CNS Tumors Unit, Medical University of Vienna, Vienna, Austria.9 Department of Medicine I, Medical University of Vienna, Vienna, Austria.8 Institute of Neurology, Medical University of Vienna, Vienna, Austria.7 Department of Pathology, Stanford University, Stanford, California.6 Department of Biochemistry, Stanford University, Stanford, California.5 Program in Biomedical Informatics, Stanford University, Stanford, California.4 Biophysics Program, Stanford University, Stanford, California.3 Department of Pediatrics, Stanford University, Stanford, California.2 Department of Genetics, Stanford University, Stanford, California.1 Cancer Biology Program, Stanford University, Stanford, California.