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@ARTICLE{Mhrmann:153784,
      author       = {L. Möhrmann$^*$ and M. K. Zowada and H. Strakerjahn and C.
                      Siegl and A. Kopp-Schneider$^*$ and D. Krunic$^*$ and D.
                      Strunk and M. Schneider and M. Kriegsmann and K. Kriegsmann
                      and F. Herbst and C. R. Ball and H. Glimm$^*$ and S.
                      Dieter$^*$},
      title        = {{A} {P}erivascular {N}iche in the {B}one {M}arrow {H}osts
                      {Q}uiescent and {P}roliferating {T}umorigenic {C}olorectal
                      {C}ancer {C}ells.},
      journal      = {International journal of cancer},
      volume       = {147},
      number       = {2},
      issn         = {1097-0215},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2020-00450},
      pages        = {519-531},
      year         = {2020},
      note         = {2020 Jul 15;147(2):519-531 / #EA:B280#LA:B280#},
      abstract     = {Disseminated tumor cells (dTCs) can frequently be detected
                      in the bone marrow (BM) of colorectal cancer (CRC) patients,
                      raising the possibility that the BM serves as a reservoir
                      for metastatic tumor cells. Identification of dTCs in BM
                      aspirates harbors the potential of assessing therapeutic
                      outcome and directing therapy intensity with limited risk
                      and effort. Still, the functional and prognostic relevance
                      of dTCs is not fully established. We have previously shown
                      that CRC cell clones can be traced to the bone marrow (BM)
                      of mice carrying patient-derived xenografts. However,
                      cellular interactions, proliferative state and
                      tumorigenicity of dTCs remain largely unknown. Here, we
                      applied a co-culture system modeling the microvascular niche
                      and used immunofluorescence imaging of the murine BM to show
                      that primary CRC cells migrate towards endothelial tubes.
                      dTCs in the BM were rare, but detectable in mice with
                      xenografts from most patient samples (8/10) predominantly at
                      perivascular sites. Comparable to primary tumors, a
                      substantial fraction of proliferating dTCs were detected in
                      the BM. However, most dTCs were found as isolated cells,
                      indicating that dividing dTCs rather separate than aggregate
                      to metastatic clones - a phenomenon frequently observed in
                      the microvascular niche model. Clonal tracking identified
                      subsets of self-renewing tumor-initiating cells in the BM
                      that formed tumors out of BM transplants, including one
                      subset that did not drive primary tumor growth. Our results
                      indicate an important role of the perivascular BM niche for
                      CRC cell dissemination and show that dTCs can be a potential
                      source for tumor relapse and tumor heterogeneity. This
                      article is protected by copyright. All rights reserved.},
      cin          = {B280 / C060 / W210 / DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B280-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)W210-20160331 / I:(DE-He78)DD01-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32077087},
      doi          = {10.1002/ijc.32933},
      url          = {https://inrepo02.dkfz.de/record/153784},
}