Researchers at Weill Cornell Medicine have made a significant discovery regarding the systemic effects of tumors on the liver.
They found that a wide range of tumor types can remotely reprogram the liver, leading to a condition similar to fatty liver disease.
These findings shed light on how tumors survive and progress, while also suggesting new possibilities for detecting and reversing these effects.
Tumor-Induced Changes in the Liver
In a study published in Nature, scientists investigated how tumors cause changes in the liver.
They identified that tumors release extracellular vesicles and particles (EVPs) containing fatty acids, which reprogram the liver to resemble fatty liver disease.
This phenomenon was observed in animal models and the livers of human cancer patients.
Implications for Liver Function and Drug Metabolism
The reprogrammed liver showed signs of inflammation and a decrease in cytochrome P450 enzymes responsible for drug metabolism.
The inflammation was characterized by elevated levels of tumor necrosis factor-α (TNF-α). The reduction in drug-metabolizing enzymes may explain why cancer patients become less tolerant to chemotherapy and other drugs over time.
EVPs and Liver Reprogramming
The researchers found that the reprogramming of the liver was initiated by EVPs released by distant tumors. These EVPs carried fatty acids, particularly palmitic acid.
When liver-resident immune cells called Kupffer cells took up the fatty acid cargo, they triggered the production of TNF-α, resulting in fatty liver formation.
Clinical Relevance and Potential Interventions
Although the study primarily utilized animal models, similar liver changes were observed in newly diagnosed pancreatic cancer patients who later developed non-liver metastases.
The researchers believe that blocking tumor-EVP release, inhibiting the packaging of palmitic acid into EVPs, suppressing TNF-α activity, or eliminating Kupffer cells could mitigate the systemic effects of tumors on the liver.
Advancing Treatment and Detection
The study opens up possibilities for developing new tests and drugs to detect and reverse the effects of tumor-induced liver reprogramming.
Strategies to counteract these effects could improve treatment outcomes for cancer patients.
Additionally, the detection of palmitic acid in tumor EVPs circulating in the blood may serve as a potential warning sign of advanced cancer.
Unveiling Tumor Survival Mechanisms
The study highlights how tumors can pathologically alter the liver, leading to a condition resembling fatty liver disease.
The discovery of tumor-induced liver reprogramming provides insights into cancer’s survival mechanisms.
By understanding and targeting these effects, researchers hope to develop innovative approaches to detect, prevent, and treat the systemic complications caused by tumors.
If you care about liver health, please read studies about new promising drug for pancreatic and liver cancer, and how sugary beverages affects the liver.
For more information about liver health, please see recent studies about a new therapy for fatty liver disease, and results showing oats and rye brans can protect your gut and liver health.
The study was published in Nature.
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