Cancer Cells 'Transform' to Adapt to the Organs They Spread To... Weakness Found in Liver-Metastatic Colorectal Cancer [Health LAB]

[Financial News] Cancer cells have been found to change the way they survive when they move to another organ, adapting to the environment there. South Korean researchers recreated the environment in which cancer spreads to other organs and identified this early adaptation process. They also confirmed that colorectal cancer cells that have metastasized to the liver are vulnerable to drugs that block a specific protein. The researchers additionally identified a protein that could serve as an Achilles' heel for liver-metastatic colorectal cancer, raising hopes for the development of personalized drugs to inhibit cancer metastasis.
According to Ulsan National Institute of Science and Technology (UNIST) on the 22nd, a team led by Seung Woo Cho and Tae-eun Park, professors in UNIST's Department of Biomedical Engineering, developed a culture system that recreates the tissues surrounding different organs. The team identified the early adaptation process of colorectal cancer cells during metastasis, as well as vulnerabilities in colorectal cancer that has spread to the liver.
The researchers recreated in the laboratory an environment similar to the one cancer cells encounter after metastasizing to an actual organ. They removed the cells from organs, leaving only the extracellular matrix, and made it into a gel into which they inserted patient-derived colorectal cancer cells.
The extracellular matrix not only surrounds and supports cells but also interacts with receptors on the cell surface, affecting cell growth and survival. Its composition also varies from one organ to another. The researchers used the colon, liver, lungs and brain of pigs—whose tissue composition is similar to that of humans and can be obtained in sufficient quantities—to create four types of culture materials.
The experiments showed that even the same colorectal cancer cells formed tumor masses to different extents and exhibited different epigenetic changes regulating gene activity, depending on the culture material from each organ in which they were grown. This indicates that when cancer cells arrive in a new organ, they adapt to survive by changing how certain genes function in response to the surrounding environment.
In the environment recreating liver tissue, production of the protein hepatocyte nuclear factor 4 alpha (HNF4A), which regulates gene activity, increased. When HNF4A was suppressed, the rate at which small tumor masses formed also fell sharply.
The researchers also discovered another vulnerability in colorectal cancer cells adapted to the liver environment. When they administered a drug that blocks c-MET, a protein that acts as a receptor for cell-survival signals, the cancer cells' survival rate dropped significantly. In contrast, the same drug produced only a minimal response under standard culture conditions.
This suggests that drug vulnerabilities that are not readily apparent when cancer cells are studied on their own can emerge when the environment of the organ to which they have spread is recreated. The researchers believe c-MET could be a potential therapeutic target for liver-metastatic colorectal cancer.
The research team explained, "The process by which cancer cells adapt immediately after arriving in another organ is an important gateway that determines whether metastasis succeeds, but it has been difficult to study because patients are often diagnosed only after tumors have already formed. This study recreated the tissues surrounding different organs and showed that gene activity and survival strategies can vary depending on where cancer cells take hold."
The team added, "Expanding this approach to various cancer types will help develop personalized treatments that target vulnerabilities arising when a patient's cancer metastasizes to a specific organ."
UNIST researchers Heejeong Yoon and Dayoung Kim participated in the study as co-first authors. The findings were published online on August 26 in Bioactive Materials, an international journal specializing in biomaterials.



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