When colorectal cancer cells are exposed to two different types of 'forever chemicals' in the lab, the chemicals can potentially accelerate cancer progression, new research suggests.

A new study conducted an analysis of exposure levels comparable to those found in firefighters and other people who come into regular contact with per- and poly-fluoroalkyl substances (PFAS).

Firefighters' blood levels of PFAS tend to be higher than the general population's because of their frequent exposure to firefighting foam, which contains PFAS chemicals for its flame retardant properties.

Firefighters are more likely than the general population to develop and die from a variety of cancers that include colorectal cancer. Environmental factors are believed to be related to about 80 percent of CRC cases.

In the new research, PFAS exposure in the lab induced CRC cells to migrate to new positions, implying a potential role in cancer spreading (metastasis) in living organisms.

"It doesn't prove it's metastasis, but they have increased motility, which is a feature of metastasis," says Yale University epidemiologist Caroline H. Johnson.

PFAS are human-made chemicals based on carbon-fluorine bonds, and as the nickname 'forever chemicals' suggests, these bonds are very strong and resistant to degradation, which makes PFAS popular for use in many kinds of products. Unfortunately, it also allows them to survive in the environment for years in ever-increasing concentrations.

"PFAS make up a prevalent class of persistent organic pollutants of increasing public concern worldwide," says co-first author and physiologist Jie Zheng from Yale University.

"They have been frequently detected in the environment, such as in drinking water, indoor dust, cleaning products, and coatings."

Many of these 'forever chemicals' are still present in everyday items, though the hazards of PFAS are largely unclear – partially because of the many different compounds involved.

Research has shown that these long-lasting chemicals spread throughout the environment, and exposure to high levels has been linked to harmful health effects in people and animals.

Perfluorooctanoic acid (PFOA), a widely used PFAS, was classified as carcinogenic to humans by the International Agency for Research on Cancer in November 2023, and perfluorooctanesulfonic acid (PFOS), another common PFAS, was classified as possibly carcinogenic to humans.

To study how they affect aggressive CRC, Zheng, Johnson, and colleagues used lab-grown CRC cells and metabolomics – a process that measures the levels of metabolites, thousands of small molecules like amino acids, lipids, and proteins.

"We look at patterns that occur within an exposed group of people or a diseased group of people, then try to generate a hypothesis as to why somebody may develop a disease or have progression of disease," Johnson says.

"Metabolomics is one of the only tools where you can measure environmental exposures in the same sample as the biological effect."

Two CRC cell types, formed into balls called spheroids, were used in the experiments. A wild-type KRAS gene was present in one type, while the other had a common mutation in the KRAS gene, which is linked to particularly aggressive CRC.

When exposed to PFOS and PFOA, the cells showed increased movement and a higher tendency of spreading. In a different test with CRC cells grown in a flat layer, a line was scratched down the middle to split them. When the chemicals were introduced, the cells grew and moved toward each other again.

To dig deeper, the researchers examined the chemicals' effects on the cell's metabolism. PFAS exposure altered various metabolites crucial for cell function, like amino acids and fatty acids, as well as signaling proteins associated with metastasis.

Substances that are usually anti-inflammatory and protective against cancer were reduced in the CRC cells after exposure, too. Some differences were more noticeable in the mutated cells, which could mean that cancers with this mutation may be more likely to spread with exposure to PFAS.

These results in the lab indicate that exposure to high levels of PFOS and PFOA could potentially increase the risk of CRC spreading in real-life conditions. This is crucial information for those in jobs with potential high exposure, the team says, and monitoring these chemicals is key to safeguarding their health, as are future clinical studies.

"Many in vitro studies can't be translated into humans," Johnson explains, "but I think understanding first the mechanisms of how they can actually affect cancer cell growth is important."

The study has been published in Environmental Science & Technology.