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@ARTICLE{Siqin:300141,
      author       = {S. Siqin$^*$ and E. Nikitina$^*$ and M. Rahbari$^*$ and C.
                      Ernst$^*$ and D. Krunic$^*$ and E. Birgin and C. Tessmer$^*$
                      and I. Hofmann$^*$ and N. Rahbari and T. Bund$^*$},
      title        = {{B}ovine {M}eat and {M}ilk {F}actor ({BMMF}) {P}rotein {I}s
                      {E}xpressed in {M}acrophages {S}pread {W}idely over the
                      {M}ucosa of {C}olorectal {C}ancer {P}atients.},
      journal      = {Cells},
      volume       = {14},
      number       = {6},
      issn         = {2073-4409},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2025-00632},
      pages        = {455},
      year         = {2025},
      note         = {#EA:D460#LA:D460#},
      abstract     = {Red meat consumption is considered a risk factor for
                      colorectal cancer (CRC) development and stimulated isolation
                      of plasmid-like DNA molecules from bovine serum and milk,
                      termed bovine meat and milk factors (BMMFs). BMMFs encode a
                      conserved replication protein (Rep). Increased populations
                      of Rep-expressing macrophages have been identified in the
                      peritumor of CRC patients and pre-cancerous tissues when
                      compared to the tissues of healthy individuals. This
                      supports the concept that BMMFs increase cancer risk by
                      indirect carcinogenesis, upon induction of chronic
                      inflammation. However, the spread of Rep+ immune cells in
                      tissues at greater distances from primary tumors has not yet
                      been assessed. Here, we immunohistologically analyzed the
                      presence of Rep+ immune cells in sets of tumor, peritumor
                      and, additionally, distant tissues of CRC patients (n = 13).
                      We identified consistently high numbers of BMMF-positive
                      macrophages in mucosal tissues at distances of as much as 25
                      cm away from the primary tumors, at levels comparable to
                      peritumors and associated with M2-like macrophage
                      polarization. The broad distribution of BMMFs suggests that
                      BMMF+ macrophages might already exist at stages of
                      pre-cancerous dysplasia or before. Quantification of BMMF
                      tissue expression during colonoscopy might help to
                      preventively stratify individuals at risk of developing
                      polyps/CRC and recommend them for enhanced surveillance
                      and/or changes in dietary lifestyle.},
      keywords     = {Colorectal Neoplasms: metabolism / Colorectal Neoplasms:
                      pathology / Humans / Macrophages: metabolism / Animals /
                      Cattle / Female / Male / Middle Aged / Aged / Intestinal
                      Mucosa: metabolism / Intestinal Mucosa: pathology / bovine
                      meat and milk factors (Other) / chronic inflammation (Other)
                      / colorectal cancer (Other) / diet (Other) / indirect
                      carcinogenesis (Other) / macrophages (Other) / myeloid
                      immune checkpoint (Other)},
      cin          = {D460 / D440 / W210 / W170},
      ddc          = {570},
      cid          = {I:(DE-He78)D460-20160331 / I:(DE-He78)D440-20160331 /
                      I:(DE-He78)W210-20160331 / I:(DE-He78)W170-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40136704},
      pmc          = {pmc:PMC11940877},
      doi          = {10.3390/cells14060455},
      url          = {https://inrepo02.dkfz.de/record/300141},
}