With a unique approach that draws on 3D printing technologies, a team of University of Wisconsin-Madison researchers is developing new tools for understanding how ovarian cancer develops in women. A $2 million grant from the National Institutes of Health (NIH) is funding the research.
Ovarian cancer is relatively rare; about 1.5 percent of American women will be diagnosed with it in their lifetime. But it is difficult to detect in its early stages, which means doctors don’t usually diagnose ovarian cancer until late in the disease’s progression, after it has spread to other parts of the body. This is reflected in the grim outlook for most women with ovarian cancer: the five-year survival rate is about 25 percent.
Led by Paul Campagnola, a professor of biomedical engineering and medical physics at UW-Madison, the team aims to improve that outlook by understanding how ovarian cancer cells interact with nearby body tissue, and by developing new tools for imaging and detecting the disease. With the NIH funding, they’ll first use cutting-edge technologies they’ve developed on the UW-Madison campus to image tissues from surgical patients, with a keen eye on collagen.
“In most cancers, including ovarian, there are large changes in the collagen structure that goes along with the disease,” Campagnola says. “It might be first. It might be later. It’s actually not known.”
It’s one of the unknowns that Campagnola and his colleagues, including Kevin Eliceiri, director of UW-Madison’s Laboratory for Optical and Computational Instrumentation (LOCI), and Manish Patankar, associate professor of obstetrics and gynecology, hope their research illuminates.
Cue the team’s next step: They’ll use in-house fabrication technologies to essentially 3D print tiny biomimetic models of the collagen samples they’ve imaged. (Biomimetic refers to synthetic materials that mimic biological ones; think Velcro and burrs.) The biomimetic tissue models Campagnola and his team will 3D print will have to be extremely small because, after seeding them with ovarian cancer cells, they’ll implant them into mice.
Why not simply inject the mice with cancer cells and skip the painstaking imaging and 3D printing process?
Because mice don’t get ovarian cancer. And there lies a partial answer for why we still don’t understand ovarian cancer as well as many other cancers.
“The current way that people study ovarian cancer in a mouse is very poor,” Campagnola explains. “They just take human cell lines and then inject them into a mouse. Then some of them will form into a tumor, but most do not.”
By implanting a 3D tissue model seeded with ovarian cancer into mice, Campagnola hopes to mimic more closely the conditions of metastatic ovarian cancer in a human woman. The 3D structure of the models is key.
“What’s different is our tissues will already be 3D structured,” Campagnola says. “One problem when people study cancer sometimes is that they put cells in a dish. Cells in a dish don’t act like cells in tissue. So we’re trying to give them the tissue structure that cancers cells would have in a native environment.”
From there, they’ll study how the implanted tumors grow inside the mice, and hopefully begin to understand more about the cues and processes involved in the disease’s progression and further metastases. It’s an approach that no one has ever attempted.
The new approach will also help improve the imaging of ovaries inside the body. “It’s an integrated approach to improving our imaging capabilities, but then also using our imaging capabilities to make these models so we can study the biology,” Campagnola says.
Ultimately, the team’s goal is to improve screening, diagnosis and treatment of ovarian cancer. One of the most effective ways to improve the outlook for women with ovarian cancer is to develop a straightforward method for screening women at higher risk for the disease. Women with a known BRCA gene mutation—the same mutation implicated in a higher risk for breast cancer—have a 40-percent chance of developing ovarian cancer in their lifetime. “Those are the women we really want to follow,” Campagnola says. “You could imagine—we’re a long way off from this—screening those women every few years with a minimally invasive device through a laparoscope or though the fallopian tubes.”
But to get to that point, Campagnola says, researchers need to know a lot more about how ovarian cancer works. “You have to know what you’re looking for,” he says. “That’s why we have all this more basic work to do to get to that point. That’s why we need better imaging tools and we need better models to understand the biology of the disease.”
Author: Will Cushman