Professors share research about metastatic ovarian cancer, mitochondria
Martha Reilly | Monday, January 29, 2018
Broad issues relating to the detection of metastatic ovarian cancer and mitochondrial disease were placed under a magnifying glass at the College’s most recent installment of its faculty colloquium series, which took place in Madaleva Hall on Friday.
Professor of biology Calli Versagli said metastatic ovarian cancer affects thousands of women in the U.S each year, though it often goes unnoticed until it spreads or intensifies.
“What’s kind of the killer of ovarian cancer is that we don’t catch it early enough,” Versagli said. “Really only about 20 percent of those who present the illness are caught in that early stage or what we call stage one. … At stage one, the cancer is still confined to one or both of the ovaries. At stage two, typically the cancer has already spread throughout the pelvic region, and eventually, stage three is more where it’s completely gone to other parts of the abdomen, and finally, at stage four, it’s gone beyond the abdomen to other particular body parts.”
Versagli said 17 percent of those who earn an official diagnosis at stage four of the illness survive, highlighting the need for adjustments to both the detection process and the treatment effectiveness.
“I tried to understand some of the biological mechanisms behind these cells that are at this late stage, and how we could potentially target them,” she said. “One of the interesting things about this is that these cells, more or less, travel in … what we call the peritoneal fluid to these other areas within the abdominal cavity.”
Understanding the movement pattern of these cells can potentially result in advancements regarding treatment, Versagli said.
“These cells — typically epithelial cells — remain attached to your organs, and if they were floating around in other places, that really wouldn’t be healthy,” she said. “My question really is … how do epithelial ovarian cancer cells survive in this free-floating environment that they encounter to travel to these secondary sites?”
Versagli said she believes antioxidant enzymes, which function within the cell to maintain balance, have a role to play.
“These enzymes are increased in expression, meaning that there is a higher abundance of them in higher-grade tumors,” she said. “Their involvement in metastasis and the spreading … hasn’t been studied at all. So that’s really my major objective in my lab.”
To achieve this ambition, Versagli said she obtained commercially-available ovarian cancer cells and put them in environments that simulate the free-floating atmosphere they encounter in metastatic ovarian cancer.
“One of the first antioxidant enzymes I looked at was catalase,” she said. “I over-expressed catalase in these cells and put them into the soft-agar assay to see how well they survive. Interestingly enough, I found that when you over-express catalase in these ovarian cancer cells, we actually have an increased [number] of colonies that form, really suggesting that these cells seem to have an advantage over others at surviving in this free floating environment.”
Conducting this research would not have been nearly as possible or as rewarding without the help of several students, she said.
“It’s been a very interesting and exciting road for us,” Versagli said.
Assistant professor of chemistry and physics Jennifer Fishovitz said a nuanced understanding of mitochondria’s purpose served as an essential component of her research about mitochondrial diseases.
“Most of the cell’s energy that it needs to perform its daily tasks is produced in the mitochondria,” Fishovitz said. “The breakdown of [adenosine triphosphate] in the cell is used to power things like muscle contraction and chemical reactions.”
Pollution, drugs, pesticides and other toxins can contribute to mitochondrial dysfunction, Fishovitz said, so studying proteins — particularly enzymes called proteases that break down other proteins — comprised a large portion of her research.
“We take a DNA sequence that encodes for the protein that we want to study, and we put it into bacteria, and we take advantage of the machinery within the E.coli to use this DNA and to convert it into many copies of our protein,” she said. “We take that protein and test its activity in a test tube.”
Mitochondrial fusion allows for the passage of information between two mitochondria at a point of cleavage, Fishovitz said.
“We want to study whether or not this cleavage event … is beneficial for the cell,” she said. “We know it’s cleaved in the cell, but we don’t know what effect it has on the cell.”
Identifying the exact site of cleavage will be beneficial in determining whether this transfer has beneficial or adverse implications.
“There are various ways that we can do this,” she said. “One of these ways is using fluorescents. We can take this peptide and, on one end, we can put a fluorescent donor. When you put energy on it, it emits fluorescents. On the other end, you put a fluorescent quencher. … When this peptide is in tact, the donor and the quencher are close enough in space that you don’t see any fluorescent emission because it’s all absorbed by the quencher.”
In the absence of adenosine triphosphate, Fishovitz said she did not observe any fluorescent emission, and in the presence of adenosine triphosphate, she said she saw an increase of fluorescents over time.
“That gives us information about how that enzyme is working,” she said. “It also gives us an experiment to test drugs that could be inhibitors of these proteins. We’re working on getting the enzymes … to a place where we can use this assay.”