In a recent study, Yale researchers found that two ” forever chemicals” prompted cancer cells to move, suggesting a potential link to cancer spreading in living organisms. The study focused on per- and polyfluoroalkyl substances (PFAS), known for their environmental persistence and resistance to breakdown. These chemicals, called “forever chemicals,” can accumulate in the human body and are recognized for their widespread presence and suspected harmful effects.
Co-first author Jie Zheng was a postdoctoral associate working in the lab of principal investigator Caroline Johnson, PhD, associate professor of epidemiology (environmental health sciences) when the research was conducted, said, “PFAS make up a prevalent class of persistent organic pollutants of increasing public concern worldwide. They have been frequently detected in the environment, such as in drinking water, indoor dust, cleaning products, and coatings.”
Chemicals like PFAS are found in newborns, sub-Arctic Indigenous communities, fish, and birds. Any level of PFAS in the body is deemed unsafe and is linked to health issues, including cancer. In November, IARC labeled PFOA as carcinogenic and PFOS as possibly carcinogenic.
No studies have explored the link between PFAS and colorectal carcinoma (CRC). Firefighters heavily exposed to PFAS have higher rates of this cancer. Around 80% of CRC cases are believed to be environmentally related.
The specific role of these chemicals in causing or promoting this type of cancer has been unclear.
The Johnson lab uses metabolomics to study colorectal cancer (CRC), measuring changes in thousands of small molecules in a sample. This helps identify patterns in exposed or diseased groups and generate hypotheses about disease development or progression. Metabolomics uniquely allows the measurement of both environmental exposures and biological effects in the same sample.
The lab immersed CRC cells in a PFAS solution for up to 7 days in experiments. They observed increased cell movement and metabolic changes consistent with the spread of cancer. These results align with the current understanding of CRC metabolism, spread, and prognosis, proving that PFAS can induce metastasis.
The study explored the impact of PFOS and PFOA, commonly found in firefighting foam and various products, on the metabolic profile of colorectal cancer (CRC) cells. Using two types of CRC cells, researchers observed increased cell migration and a tendency to spread and penetrate membranes when exposed to these chemicals. In a different experiment, cells separated by a scratch grew and migrated back together after PFAS exposure.
Although not definitive proof of metastasis, the heightened cell motility suggests a metastatic feature. Metabolomic analysis revealed the production of fatty acids, amino acids, and signaling proteins, aligning with patterns linked to metastasis. Notably, protective small-chain fatty acids were downregulated.
A Western blot analysis revealed distinct changes in signal proteins linked to metastasis during the epithelial-mesenchymal transition (EMT). When exposed to higher levels of either PFOS or PFOA, both cell types showed reduced expression of E-cadherin, making them less adhesive—a crucial step in EMT-related metastasis. These findings increased confidence that the cells behaved like metastatic cells in the body.
Notably, the changes indicating metastatic potential were more pronounced in the KRAS-mutated cell line. This suggests that cancers with this mutation may be particularly susceptible to spreading after exposure to these chemicals.
The research is part of an ongoing effort to understand the exposome, encompassing all environmental influences on a person throughout life. This includes biological, chemical, ecological, and social factors. PFAS, being widespread, results in almost universal exposure.
The study replicated exposure levels found in firefighters and others regularly in contact with PFAS, like those near landfills, airports, military bases, or wastewater treatment plants. Future research by the Johnson lab intends to examine lower, everyday exposure levels and investigate PFAS levels in colorectal cancer patients and their clinical outcomes.
Johnson said, “Many in vitro studies can’t be translated into humans. But I think understanding the mechanisms of how they can affect cancer cell growth is important.”
The Yale study concludes that exposure to “forever chemicals” known as PFAS, specifically PFOS and PFOA, promotes the migration of cancer cells, indicating a potential link between these chemicals and the spread of cancer. The findings highlight the need for further research to understand the health risks associated with PFAS exposure, especially cancer cell behavior.
Journal reference:
- Jie Zheng, Boshi Sun, et al., Perfluorooctanesulfonic Acid and Perfluorooctanoic Acid Promote Migration of Three-Dimensional Colorectal Cancer Spheroids. Environmental Science & Technology. DOI: 10.1021/acs.est.3c04844.