TY  - JOUR
AU  - Siqin, Sumen
AU  - Nikitina, Ekaterina
AU  - Rahbari, Mohammad
AU  - Ernst, Claudia
AU  - Krunic, Damir
AU  - Birgin, Emrullah
AU  - Tessmer, Claudia
AU  - Hofmann, Ilse
AU  - Rahbari, Nuh
AU  - Bund, Timo
TI  - Bovine Meat and Milk Factor (BMMF) Protein Is Expressed in Macrophages Spread Widely over the Mucosa of Colorectal Cancer Patients.
JO  - Cells
VL  - 14
IS  - 6
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DKFZ-2025-00632
SP  - 455
PY  - 2025
N1  - #EA:D460#LA:D460#
AB  - 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.
KW  - Colorectal Neoplasms: metabolism
KW  - Colorectal Neoplasms: pathology
KW  - Humans
KW  - Macrophages: metabolism
KW  - Animals
KW  - Cattle
KW  - Female
KW  - Male
KW  - Middle Aged
KW  - Aged
KW  - Intestinal Mucosa: metabolism
KW  - Intestinal Mucosa: pathology
KW  - bovine meat and milk factors (Other)
KW  - chronic inflammation (Other)
KW  - colorectal cancer (Other)
KW  - diet (Other)
KW  - indirect carcinogenesis (Other)
KW  - macrophages (Other)
KW  - myeloid immune checkpoint (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40136704
C2  - pmc:PMC11940877
DO  - DOI:10.3390/cells14060455
UR  - https://inrepo02.dkfz.de/record/300141
ER  -