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@ARTICLE{Akram:125421,
      author       = {I. G. Akram$^*$ and R. Georges$^*$ and T. Hielscher$^*$ and
                      H. Adwan$^*$ and M. Berger$^*$},
      title        = {{T}he chemokines {CCR}1 and {CCRL}2 have a role in
                      colorectal cancer liver metastasis.},
      journal      = {Tumor biology},
      volume       = {37},
      number       = {2},
      issn         = {1423-0380},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2017-01551},
      pages        = {2461 - 2471},
      year         = {2016},
      abstract     = {C-C chemokine receptor type 1 (CCR1) and chemokine C-C
                      motif receptor-like 2 (CCRL2) have not yet been sufficiently
                      investigated for their role in colorectal cancer (CRC).
                      Here, we investigated their expression in rat and human CRC
                      samples, their modulation of expression in a rat liver
                      metastasis model, as well as the effects on cellular
                      properties resulting from their knockdown. One rat and five
                      human colorectal cancer cell lines were used. CC531 rat
                      colorectal cells were injected via the portal vein into rats
                      and re-isolated from rat livers after defined periods.
                      Following mRNA isolation, the gene expression was
                      investigated by microarray. In addition, all cell lines were
                      screened for mRNA expression of CCR1 and CCRL2 by reverse
                      transcription polymerase chain reaction (RT-PCR). Cell lines
                      with detectable expression were used for knockdown
                      experiments; and the respective influence was determined on
                      the cells' proliferation, scratch closure, and colony
                      formation. Finally, specimens from the primaries of 50
                      patients with CRC were monitored by quantitative RT-PCR for
                      CCR1 and CCRL2 expression levels. The microarray studies
                      showed peak increases of CCR1 and CCRL2 in the early phase
                      of liver colonization. Knockdown was sufficient at mRNA but
                      only moderate at protein levels and resulted in modest but
                      significant inhibition of proliferation (p < 0.05),
                      scratch closure, and colony formation (p < 0.05). All
                      human CRC samples were positive for CCR1 and CCRL2 and
                      showed a significant pairwise correlation (p < 0.0004),
                      but there was no correlation with tumor stage or age of
                      patients. In summary, the data point to an important role of
                      CCR1 and CCRL2 under conditions of organ colonization and
                      both chemokine receptors qualify as targets of treatment
                      during early colorectal cancer liver metastasis.},
      keywords     = {RNA, Messenger (NLM Chemicals) / Receptors, CCR (NLM
                      Chemicals)},
      cin          = {G401 / C060},
      ddc          = {570},
      cid          = {I:(DE-He78)G401-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26383527},
      doi          = {10.1007/s13277-015-4089-4},
      url          = {https://inrepo02.dkfz.de/record/125421},
}