Structural expression of bovine milk and meat factors in tissues of colorectal, lung and pancreatic cancer patients

Chronic inflammation, linked to the presence of bovine milk and meat factors (BMMFs) and specific subsets of macrophages, results in oxygen radical synthesis and induction of mutations in DNA of actively replicating cells and replicating single stranded DNA. Cancers arising from this process have been characterized as indirect carcinogenesis by infectious agents (without persistence of genes of the agent in premalignant or cancers cells). Here, we investigate structural properties of pleomorphic vesicles, regularly identified by staining peritumor tissues of colorectal, lung and pancreatic cancer for expression of BMMF Rep. The latter represents a subgroup of BMMF1 proteins involved in replication of small single‐stranded circular plasmids of BMMF, but most likely also contributing to pleomorphic vesicular structures found in the periphery of colorectal, lung and pancreatic cancers. Structurally dense regions are demonstrated in preselected areas of colorectal cancer, after staining with monoclonal antibodies against BMMF1 Rep. Similar structures were observed in human embryonic cells (HEK293TT) overexpressing Rep. These data suggest that Rep or Rep isoforms contribute to the structural formation of vesicles.

[1]  P. Meltzer,et al.  Evidence for virus-mediated oncogenesis in bladder cancers arising in solid organ transplant recipients , 2023, eLife.

[2]  G. Sutter,et al.  Identification and Characterization of Circular Single-Stranded DNA Genomes in Sheep and Goat Milk , 2021, Viruses.

[3]  E. de Villiers,et al.  Bovine Meat and Milk Factors (BMMFs): Their Proposed Role in Common Human Cancers and Type 2 Diabetes Mellitus , 2021, Cancers.

[4]  G. Sutter,et al.  Circular Rep-Encoding Single-Stranded DNA Sequences in Milk from Water Buffaloes (Bubalus arnee f. bubalis) , 2021, Viruses.

[5]  E. de Villiers,et al.  Analysis of chronic inflammatory lesions of the colon for BMMF Rep antigen expression and CD68 macrophage interactions , 2021, Proceedings of the National Academy of Sciences.

[6]  C. von Kalle,et al.  Comprehensive genomic characterization of gene therapy-induced T-cell acute lymphoblastic leukemia , 2020, Leukemia.

[7]  Michael J. Tisza,et al.  Discovery of several thousand highly diverse circular DNA viruses , 2019, bioRxiv.

[8]  G. Schmitz,et al.  Exosomes of pasteurized milk: potential pathogens of Western diseases , 2019, Journal of Translational Medicine.

[9]  E. de Villiers,et al.  A specific class of infectious agents isolated from bovine serum and dairy products and peritumoral colon cancer tissue , 2019, Emerging microbes & infections.

[10]  H. zur Hausen,et al.  Specific nutritional infections early in life as risk factors for human colon and breast cancers several decades later , 2018, International journal of cancer.

[11]  E. de Villiers,et al.  Isolation of Two Virus-Like Circular DNAs from Commercially Available Milk Samples , 2017, Genome Announcements.

[12]  E. de Villiers,et al.  Cancer "causation" by infections--individual contributions and synergistic networks. , 2014, Seminars in oncology.

[13]  Kunihiko Sadakane,et al.  MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph , 2014, Bioinform..

[14]  E. de Villiers,et al.  Isolation of Protein-Associated Circular DNA from Healthy Cattle Serum , 2014, Genome Announcements.

[15]  E. de Villiers,et al.  Mycovirus-Like DNA Virus Sequences from Cattle Serum and Human Brain and Serum Samples from Multiple Sclerosis Patients , 2014, Genome Announcements.

[16]  E. de Villiers,et al.  Novel Replication-Competent Circular DNA Molecules from Healthy Cattle Serum and Milk and Multiple Sclerosis-Affected Human Brain Tissue , 2014, Genome Announcements.

[17]  Steven L Salzberg,et al.  Fast gapped-read alignment with Bowtie 2 , 2012, Nature Methods.

[18]  E. de Villiers,et al.  The Diversity of Torque Teno Viruses: In Vitro Replication Leads to the Formation of Additional Replication-Competent Subviral Molecules , 2011, Journal of Virology.

[19]  H. Hausen,et al.  The search for infectious causes of human cancers: where and why. , 2009, Virology.

[20]  J. Slot,et al.  Cryosectioning and immunolabeling , 2007, Nature Protocols.

[21]  D. Lowy,et al.  Efficient Intracellular Assembly of Papillomaviral Vectors , 2004, Journal of Virology.

[22]  E. de Villiers,et al.  Infectious Agents in Bovine Red Meat and Milk and Their Potential Role in Cancer and Other Chronic Diseases. , 2017, Current topics in microbiology and immunology.

[23]  E. de Villiers,et al.  Dairy cattle serum and milk factors contributing to the risk of colon and breast cancers , 2015, International journal of cancer.

[24]  D. Lowy,et al.  Generation of HPV pseudovirions using transfection and their use in neutralization assays. , 2005, Methods in molecular medicine.