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ABSTRACT Bivalve transmissible neoplasias (BTNs) are leukemia-like cancers found in at least 10 bivalve species, in which the cancer cells themselves transfer from one individual to another, spreading as an unusual form of infectious disease. Before the infectious etiology was known, there were reports of lethality and outbreaks of cancer in the soft-shell clam (Mya arenaria) on the east coast of North America. Using sensitive and specific qPCR assays, we followed the progression of BTN in naturally-infected soft-shell clams from Maine, USA. We observed variable outcomes, with about half of clams (9/21) progressing to high levels of cancer and death, about half exhibiting long-term non-progression (11/21), and a single animal showing regression of cancer. We also observe a significant decrease in survival in animals that progress to >10% cancer in their hemolymph, while we see no effect on survival in clams with BTN that are long-term non-progressors. As most bivalves do not physically contact each other, and BTN cells can survive in seawater, it has been proposed that BTN is spread through release of cancer cells into the water. We used qPCR to detect BTN-specific DNA in environmental DNA (eDNA) in the tanks of animals throughout this experiment. We show that cancer cell release can be detected in tank water of most clams with >24% cancer in their hemolymph, but not below this level. Cancer cell release is variable and occurs in bursts, but above 24% detection in eDNA correlates with progression of cancer in the hemolymph. This study demonstrates both the lethality of BTN and the presence of a block to the progression of BTN in a large portion of clams in a population with enzootic disease. This also further supports the hypothesis that BTN cells transmit through seawater and provides insights into the mechanisms of the transmission dynamics.
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Survival and Detection of Bivalve Transmissible Neoplasia from the Soft-Shell Clam Mya arenaria (MarBTN) in Seawater
Many pathogens can cause cancer, but cancer itself does not normally act as an infectious agent. However, transmissible cancers have been found in a few cases in nature: in Tasmanian devils, dogs, and several bivalve species. The transmissible cancers in dogs and devils are known to spread through direct physical contact, but the exact route of transmission of bivalve transmissible neoplasia (BTN) has not yet been confirmed. It has been hypothesized that cancer cells from bivalves could be released by diseased animals and spread through the water column to infect/engraft into other animals. To test the feasibility of this proposed mechanism of transmission, we tested the ability of BTN cells from the soft-shell clam (Mya arenaria BTN, or MarBTN) to survive in artificial seawater. We found that MarBTN cells are highly sensitive to salinity, with acute toxicity at salinity levels lower than those found in the native marine environment. BTN cells also survive longer at lower temperatures, with 50% of cells surviving greater than 12 days in seawater at 10 °C, and more than 19 days at 4 °C. With one clam donor, living cells were observed for more than eight weeks at 4 °C. We also used qPCR of environmental DNA (eDNA) to detect the presence of MarBTN-specific DNA in the environment. We observed release of MarBTN-specific DNA into the water of laboratory aquaria containing highly MarBTN-diseased clams, and we detected MarBTN-specific DNA in seawater samples collected from MarBTN-endemic areas in Maine, although the copy numbers detected in environmental samples were much lower than those found in aquaria. Overall, these data show that MarBTN cells can survive well in seawater, and they are released into the water by diseased animals. These findings support the hypothesis that BTN is spread from animal-to-animal by free cells through seawater.
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- Award ID(s):
- 1849227
- PAR ID:
- 10403938
- Date Published:
- Journal Name:
- Pathogens
- Volume:
- 11
- Issue:
- 3
- ISSN:
- 2076-0817
- Page Range / eLocation ID:
- 283
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/pathogens11030283
