Researchers from North Carolina State University have found a very high prevalence of Bartonella bacteria in tumors and tissues - but not blood samples - taken from dogs with hemangiosarcoma, a cancer of the blood vessels. The work further supports the connection between persistent infection and some types of cancer and adds to the evidence that Bartonella can remain and thrive, undetected, within tissue.
Hemangiosarcoma (HSA) is an aggressive, deadly cancer that arises from cells lining the blood vessels. It is responsible for two-thirds of all heart or splenic tumors in dogs, and is most common in medium-sized and middle-aged dogs. Since HSA usually cannot be diagnosed without major abdominal surgery, most HSA remains undetected until it has reached an advanced stage, resulting in a one-year survival rate of only 12 to 20%.
"There are clear precedents for the involvement of bacterial infections in tumor development," says Ed Breitschwerdt, Melanie S. Steele Distinguished Professor of Medicine at NC State's College of Veterinary Medicine and corresponding author of a paper describing the work. "Given the established links between chronic inflammation and cancer, we wanted to determine whether chronic infection of blood vessels due to bacteria could be a contributing cause of this cancer."
Breitschwerdt and colleagues from NC State looked at tumor tissue, non-tumor tissue and blood samples from 110 dogs with HSA from across the U.S. They screened both the tissues and the blood for Bartonella, Babesia, and Mycoplasma, three bacteria associated specifically with blood infections.
Bartonella DNA was amplified and sequenced from 80 of the dogs with HSA: it was present in 34% of tumor tissue and 63% of non-tumor tissue, but appeared in none of the blood samples. Mycoplasma DNA was only amplified from 5 of the dogs and Babesia wasn't detected in any dog.
"Research in recent years has confirmed that persistent infection with or inflammation caused by stealth pathogens is a risk factor for developing cancer later in life," Breitschwerdt says. "With the exception of Helicobacter pylori, the emphasis on evaluating the relationship between infection and cancer has focused on viruses. But intracellular bacterial pathogens such as Bartonella may also play an important and previously uninvestigated role.
"Bartonella is a stealth pathogen - it can 'hide' in the cells that line blood vessel walls, which is part of what makes it so difficult to detect," Breitschwerdt says. "This work adds more evidence to the connection between infection and cancer risk, and demonstrates that molecular testing of whole blood samples does not rule out the tissue presence of this pathogen. Future studies are needed to investigate whether Bartonella infection can be a cause of HSA. Our team will be focusing on creating more sensitive diagnostic testing as part of this effort."
The work appears in PLOS ONE and was supported by the American Kennel Club Canine Health Foundation (Grant 2519) and the Comparative Medicine and Translational Research Program of the National Institutes of Health (T32OD011130). Ph.D. student Erin Lashnits is first author.
Note to editors: An abstract follows.
"Molecular prevalence of Bartonella, Babesia, and hemotropic Mycoplasma species in dogs with hemangiosarcoma from across the United States"
Authors: Erin Lashnits, Pradeep Neupane, Julie Bradley, Toni Richardson, Rachael Thomas, Keith Linder, Matthew Breen, Ricardo Maggi, Ed Breitschwerdt, North Carolina State University
Published: Online Jan. 10, 2020 in PLOS ONE
Hemangiosarcoma (HSA), a locally invasive and highly metastatic endothelial cell neoplasm, accounts for two-thirds of all cardiac and splenic neoplasms in dogs. Bartonella spp. infection has been reported in association with neoplastic and non-neoplastic vasoproliferative lesions in animals and humans. The objective of this study was to determine the prevalence of Bartonella spp. in conjunction with two other hemotropic pathogens, Babesia spp. and hemotropic Mycoplasma spp., in tissues and blood samples from 110 dogs with histopathologically diagnosed HSA from throughout the United States. This was a retrospective, observational study using clinical specimens from 110 dogs with HSA banked by the biospecimen repository of the Canine Comparative Oncology and Genomics Consortium. Samples provided for this study from each dog included:fresh frozen HSA tumor tissue (available from n = 100 of the 110 dogs), fresh frozen non-tumor tissue (n = 104), and whole blood and serum samples (n = 108 and 107 respectively). . Blood and tissues were tested by qPCR for Bartonella, hemotropic Mycoplasma, and Babesia spp. DNA; serum was tested for Bartonella spp. antibodies. Bartonella spp. DNA was amplified and sequenced from 73% of dogs with HSA (80/110). In contrast, hemotropic Mycoplasma spp. DNA was amplified from a significantly smaller proportion (5%, p<0.0001) and Babesia spp. DNA was not amplified from any dog. Of the 100 HSA tumor samples submitted, 34% were Bartonella PCR positive (32% of splenic tumors, 57% of cardiac tumors, and 17% of other tumor locations). Of 104 non-tumor tissues, 63% were Bartonella PCR positive (56% of spleen samples, 93% of cardiac samples, and 63% of skin/subcutaneous samples). Of dogs with Bartonella positive HSA tumor, 76% were also positive in non-tumor tissue. Bartonella spp. DNA was not PCR amplified from whole blood. This study documented a high prevalence of Bartonella spp. DNA in dogs with HSA from geographically diverse regions of the United States. While 73% of all tissue samples from these dogs were PCR positive for Bartonella DNA, none of the blood samples were, indicating that whole blood samples do not reflect tissue presence of this pathogen. Future studies are needed to further investigate the role of Bartonella spp. in the development of HSA.