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| Home > Publications database > Lung Cancer Patients Display Increased Expression of Bovine Meat and Milk Factor (BMMF) Proteins in Peritumor Alveolar Macrophages. |
| Journal Article | DKFZ-2026-01309 |
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2026
Wiley-Liss
Bognor Regis
Abstract: Besides smoking and exposure to specific environmental risk factors, also diet and in particular red meat consumption/exposure are described as risk factors contributing to lung cancer development. Incidence of non-smoking associated lung cancer is rising rapidly, globally. Global epidemiology supports an association between lung cancer incidence and consumption of bovine products. The search for meat-/milk-associated cancer risk factors led to the isolation of plasmid DNA termed Bovine Meat and Milk Factors (BMMFs). Due to detection of increased expression levels of a conserved BMMF-encoded protein (Rep) in tissues of colorectal cancer patients, BMMFs have been proposed as causal risk factors for cancer acting via inflammation-driven indirect carcinogenesis. Yet, their presence and possible contribution to lung cancer remained elusive. In this study, Rep expression was quantified in paired tumor/peritumor tissues from lung cancer patients (n = 35) as well as cancer-free individuals (n = 19, tissues adjacent to benign hamartoma) by immunohistochemistry, co-immunofluorescence microscopy, immunodetection/mass spectroscopy and genomics/transcriptomics screening. In all patients tested, Rep expression was immunohistochemically observed in CD68+ CD163+ alveolar lung macrophages, which were present at higher numbers in peritumor tissues of cancer patients compared to controls. Expression was inversely correlated with smoking intensity, supporting BMMFs' function as a new, smoking-independent biomarker and possible driver for lung cancer. BMMF+ macrophages revealed a cancer-promoting M2-like phenotype upon scRNA-seq, suggesting BMMF as target for both prevention and therapy. BMMFs might contribute to lung cancer by inducing pro-tumorigenic macrophage populations and serve as marker for (early) cancer detection and prevention.
Keyword(s): bovine meat and milk factors ; chronic inflammation ; dietary cancer risk factors ; indirect carcinogenesis ; lung cancer
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