Cancer is one of the leading causes of deaths worldwide, not just for humans but for many animal species. PhD candidate Arianna Bartlett studies feline mammary cancer, a disease in cats that resembles human breast cancer. Cats have a high rate of mammary cancer, yet little effective treatment has been developed for them.
“Upon diagnosis, 85 percent of feline mammary tumors are malignant,” Bartlett says. “Veterinarians don't even want to take a sample of the tumor because it's possible that just touching it could make the cells spread. The only substantial ways we have to treat this cancer are surgery and chemotherapy, but the prognosis is still really poor. This is partly due to the fact that we just do not have a good understanding of how feline mammary cancer develops and progresses.”
Bartlett looks at the disease through a genetic lens. She specifically studies microRNAs, which are small RNAs that regulate gene expression, and their role in the progression of feline mammary cancer.
But how do we protect our cats and reduce the risk of feline mammary cancer? Bartlett says the best preventative is to have your animals spayed.
“We share a similar environment with our cats. They live in our houses, so they're exposed to a similar level of carcinogens as us. But really, the biggest risk factor for feline mammary cancer is not spaying your cat. If you do not spay your cat before or around the time they hit puberty, they have a dramatically increased risk of developing mammary cancer. This is the same for dogs,” she says.
Cancer Susceptibility in Cell Cultures
Bartlett works in the Van de Walle lab in the graduate field of Genetics, Genomics and Development, where she takes a comparative approach, analyzing the differences between feline cells and cells of other animals such as horses. This method allows Bartlett to gain a greater understanding of the overall progression of mammary cancer across different species, figuring out what enhances or inhibits the disease.
“Felines and humans have a very high incidence of mammary cancer, whereas other species have very low incidences. For example, since the early 1900s, there are only around 10 reported cases of equine or horse mammary cancer, in spite of the fact that horses live a long time and cancer is generally a disease of aging. We employ this comparative species approach to see why certain animals get mammary cancer and why others don't,” Bartlett says.
Using cell culture, a process to measure cell growth in Petri dishes, Bartlett exposes cells from horses and cats to a specific carcinogen called dimethylbenz(a)anthracene (DMBA), an agent that is known to induce mammary cancer. She then compares the cells’ responses.
“The cat cells repair the carcinogen-induced damage, and so the cells stay alive. But if this repair is not perfect, it allows for mutations that can eventually lead to mammary cancer arising.”
“The horse cells have this super robust response to this carcinogen. Basically, the cells die in response to the DNA damage induced by DMBA. If the cells are gone, then they can’t accumulate mutations to become a cancerous cell in the future. In contrast, the cat cells repair the carcinogen-induced damage, and so the cells stay alive. But if this repair is not perfect, it allows for mutations that can eventually lead to mammary cancer arising,” she says.
Organoids: New Approach, Enhanced Accuracy
Bartlett has taken her research further by developing three-dimensional mini-organs, known as organoids, from mammary tissues. Organoids represent the body better than traditional cell-culture methods. “Instead of having a monolayer of [horse or cat] cells [as in cell culture], I’ve developed organoids that resemble the organs you see inside the body.” Bartlett says. “This method has more accurate cell-to-cell interactions.”
Once the organoids are fully grown, Bartlett treats them with DMBA and measures their responses to see whether the carcinogen inhibits or induces mammary cancer cells. Bartlett believes the key to finding what makes mammary cancer so prevalent in some animals is finding out what makes it uncommon in others.
“Most people will say that horses don’t get mammary cancer as much because they're vegetarian, or that cows don’t because they have so many offspring throughout their lifetime. But there's just so many other things to consider. Our lab is particularly interested in the inherent differences in the animals themselves on a genetic level,” she says.
Bartlett’s work is not only meant to contribute to the possible reduction in the rate of feline mammary cancer but to have a positive impact on human breast cancer as well.
“With the research that I’m doing, we can also potentially translate our findings and the alternative treatments we may develop to human medicine. Because there are forms of human breast cancer, like triple negative breast cancer, that currently do not have effective treatments,” Bartlett says.
Uncommon Model Organisms
Bartlett’s constant development of research techniques is a response to the challenge of working with uncommon animal models.
“There is definitely a lot of difficulties that arise when studying these nontraditional model organisms. We have so many excellent technologies for more common models, so on the nontraditional side of things, we have to come up with a lot of troubleshooting, optimization, and many times, developing our own tools,” she says.
Bartlett has always worked with nontraditional animal models, starting with rainbow trout during her undergraduate years at the College of Southern Idaho, then expanding to marine worms, pigs, cows, and now cats and horses.
“I've always been outside of the traditional scientific realm. I live at the intersection of many different identities. Personally, I guess I would say I’m a little weird, which is kind of what drew me towards focusing mainly on working with nontraditional organisms in the first place,” Bartlett says.
Bartlett believes that studying nontraditional organisms can reveal more about species-specific structures that can make a certain species more or less susceptible to disease. This approach can prove to be beneficial for a variety of animals as well as humans. By comparing species that have high rates of mammary cancer, like cats and humans, to animals who have a low prevalence, such as horses and cows, Bartlett is able to see what factors may contribute to minimizing the cancer.
“Our lab is stepping in and saying that it's worth taking this unusual model, that it has applicability. Right now, [most researchers] are only studying animals that are somewhat similar to [humans] in the progression of mammary cancer, for instance, mice and rats. But by never looking at any other animals, we might miss something potentially valuable.”