A new paper published by a team that includes several Cancer Center at Illinois (CCIL) researchers demonstrates a link between per- and polyfluoroalkyl substances (PFAS) exposure and growth of testicular germ cell tumors.
PFAS chemicals, sometimes called forever chemicals because they are long-lasting and break down slowly, are found in products like clothing, furniture, adhesives, food packaging, non-stick cooking surfaces, and more. Over the years, various studies have shown a connection between PFAS chemicals and testicular cancer but have not identified what’s driving the connection.
“Testicular cancer is one of the key cancers triggered upon exposure to PFAS, and this study is the first to shed light on the mechanisms,” said Joseph Irudayaraj, CCIL Associate Director for Shared Resources. “As we progress, I am sure we will have more clarity on initiation and metastasis mechanisms.”
To examine the mechanisms between PFAS exposure and testicular germ cell tumor (TGCT) growth, a team from CCIL member Michael Spinella’s lab treated testicular cancer cell lines and mouse models with various concentrations of PFAS chemicals. Graduate student Raya Boyd led the project.
“We found that the PFAS chemicals – perfluorooctanesulfonic acid (PFOS) and HQ-115 – increase tumor growth in mice,” said Boyd.
That’s not all.
“In the cell lines, we looked at gene expression, and we found signatures associated with epigenetic markers,” said Spinella. “We happen to believe that epigenetics plays a major role in the formation of testicular cancer. Epigenetic changes are modifications to the DNA, not permanent mutations. We took the tumors out of the mice and did experiments looking at metabolism and gene expression and found changes associated with epigenetics, especially in the polycomb pathway, an epigenetic pathway we’re studying in the lab.”
Moving forward, other experiments will further concentrate on the mechanisms of TGCT growth.
“There are an estimated 12,000 PFAS chemicals, and this study only looked at three, so we have a lot more to do when it comes to this chemical class,” said Boyd. “We’re looking at testicular cancer, but that is not the endpoint of what these chemicals may be affecting when it comes to human health.”
Left to right: Ratnakar Singh, CCIL member Michael Spinella, Raya Boyd, Doha Shokry.
The team is also planning experiments to clarify how and when cancer cells start to form.
“Testicular cancer is a disease that actually starts in utero, so we’re going to treat pregnant mice with the PFAS chemicals to see if that causes any alterations in the frequency and severity of the testicular cancer that develops,” said Spinella.
His lab members are also exploring the role of AI models and machine learning. “Those can help in early diagnosis and creating better treatments for patients,” said graduate student Doha Shokry.
The team’s efforts contribute to a framework of research that Spinella has been working on for several decades.
“One of the interesting things about testicular cancer is that it can be highly curable with just standard chemotherapy, but a certain percentage of patients become resistant to that treatment,” he said.
His lab focuses on figuring out why certain patients become resistant and come up with other therapies for them.
“More studies are coming out which say toxicants are more involved in this kind of cancer than other solid cancers,” according to Ratnakar Singh, a research assistant professor and member of Spinella’s lab since 2018. “Very few research groups work in this area, so it’s important for us to study it.”
National Testicular Cancer Awareness Month
The American Cancer Society reports there will be about 9,760 new cases diagnosed this year.
Learn about detection, treatment options, and more here.
Editor’s Notes:
Michael Spinella is a professor of Comparative Biosciences at the College of Veterinary Medicine and Biomedical and Translational Sciences at the Carle Illinois College of Medicine. You can learn more about his lab and the rest of the team here.
Other CCIL collaborations on this paper include:
Joseph Irudayaraj: Professor of Bioengineering at the Grainger College of Engineering and Associate Director of the CCIL’s Shared Resources. His other affiliations can be found here.
Zeynep Madak Erdogan: Associate Professor of Food Science & Human Nutrition at the College of Agricultural, Consumer and Environmental Sciences and Associate Director for Education at the CCIL. Her other affiliations can be found here.
Funding:
This work was supported by the National Institutes of Health grant R01-CACA211875 (MJS), DOD PRCRP Impact Award W81XWH2110903 (MJS), DOD Breakthrough Award BC221269 (MJS), and Environmental Toxicology Fellowship T32 ES007326, (RIB).
Story written by Jessica Clegg, CCIL Communications Team
Video by Kamryn Grey and Jessica Clegg, CCIL Communications Team