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@ARTICLE{Sagini:166511,
      author       = {M. N. Sagini$^*$ and K. D. Klika$^*$ and A. Orry and M.
                      Zepp$^*$ and J. Mutiso$^*$ and M. Berger$^*$},
      title        = {{R}iproximin {E}xhibits {D}iversity in {S}ugar {B}inding,
                      and {M}odulates some {M}etastasis-{R}elated {P}roteins with
                      {L}ectin like {P}roperties in {P}ancreatic {D}uctal
                      {A}denocarcinoma.},
      journal      = {Frontiers in pharmacology},
      volume       = {11},
      issn         = {1663-9812},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2020-02954},
      pages        = {549804},
      year         = {2020},
      note         = {#EA:G401#LA:G401#},
      abstract     = {Riproximin (Rpx) is a type II ribosome-inactivating protein
                      with specific anti-proliferative activity. It was purified
                      from Ximenia americana by affinity chromatography using a
                      resin coupled with lactosyl residues. The same technique
                      facilitated isolation of proteins with lectin-like
                      properties from human Suit2-007 and rat ASML pancreatic
                      cancer cells, which were termed lactosyl-sepharose binding
                      proteins (LSBPs). The role of these proteins in cancer
                      progression was investigated at mRNA level using chip array
                      data of Suit2-007 and ASML cells re-isolated from nude rats.
                      These data compared significant mRNA expression changes when
                      relating primary (pancreas) and metastatic (liver) sites
                      following orthotopic and intraportal implantation of
                      Pancreatic Ductal Adenocarcinoma (PDAC) cells, respectively.
                      The affinity of Rpx to 13 simple sugar structures was
                      modeled by docking experiments, the ranking of which was
                      principally confirmed by NMR-spectroscopy. In addition, Rpx
                      and LSBPs were evaluated for anti-proliferative activity and
                      their cellular uptake was assessed by fluorescence
                      microscopy. From 13 monosaccharides evaluated, open-chain
                      rhamnose, β-d-galactose, and α-l-galactopyranose showed
                      the highest affinities for site 1 of Rpx's B-chain. NMR
                      evaluation yielded a similar ranking, as galactose was among
                      the best binders. Both, Rpx and LSBPs reduced cell
                      proliferation in vitro, but their anti-proliferative effects
                      were decreased by $15-20\%$ in the presence of galactose.
                      The program 'Ingenuity Pathway Analysis' identified 2,415
                      genes showing significantly modulated mRNA expression
                      following exposure of Suit2-007 cells to Rpx in vitro. These
                      genes were then matched to those 1,639 genes, which were
                      significantly modulated in the rat model when comparing
                      primary and metastatic growth of Suit2-007 cells. In this
                      overlap analysis, LSBP genes were considered separately. The
                      potential suitability of Rpx for treating metastatic
                      Suit2-007 PDAC cells was reflected by those genes, which
                      were modulated by Rpx in a way opposite to that observed in
                      cancer progression. Remarkably, these were $14\%$ of all
                      genes modulated during cancer progression, but $71\%$ of the
                      respective LSBP gene subgroup. Based on these findings, we
                      predict that Rpx has the potential to treat PDAC metastasis
                      by modulating genes involved in metastatic progression,
                      especially by targeting LSBPs.},
      keywords     = {Pancreatic ductal adenocarcinoma (Other) / affinity (Other)
                      / cellular lectins (Other) / lactosyl-sepharose binding
                      proteins (Other) / monosaccharides (Other) /
                      ribosome-inactivating protein (Other)},
      cin          = {G401},
      ddc          = {610},
      cid          = {I:(DE-He78)G401-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33328982},
      pmc          = {pmc:PMC7734336},
      doi          = {10.3389/fphar.2020.549804},
      url          = {https://inrepo02.dkfz.de/record/166511},
}