H. Lee Moffitt Cancer Center and Research Institute Inc.
05/28/2026 | Press release | Distributed by Public on 05/28/2026 13:15
Moffitt Study Identifies Protein that Helps Eye Cancer Spread to the Liver
GDF15, a protein that can be secreted by uveal melanoma cells, helps the cancer spread from the eye to the liver. Uveal melanoma is the most common form of eye cancer in adults.
The protein disrupts the activities of liver support cells, which, when healthy, help repair damage.
Communication between the cancer cells and liver cells generates changes to the liver's microenvironment, including promoting the growth of new blood vessels that supply tumors with the nutrients and oxygen they need to thrive.
In animal studies, shutting down GDF15 resulted in fewer and smaller liver tumors.
The study pinpoints potential new ways to stop or slow the spread of cancer from the eye to the liver.
TAMPA, Fla. - A study led by researchers at Moffitt Cancer Center helps explain why uveal melanoma, the most common form of eye cancer, often spreads to the liver. The uvea is the middle layer of the eye, including the iris. The findings, published in Cancer Research, identify an important role for tumor-derived growth differentiation factor 15 (GDF15), a stress-response signaling protein, in enabling metastasis to the liver.
Researchers found that eye cancer cells release unusually high levels of GDF15 when they reach the liver. When stellate support cells, which help repair liver damage, were exposed to the GDF15, they produced elevated levels of collagen and fibronectin, molecules that are important for normal repair. Excessive buildup, however, can create conditions that allow tumors to establish themselves within the liver.
The interaction between GDF15 and stellate cells also promoted the growth of new blood vessels that deliver oxygen and nutrients to the liver tumors, supporting their expansion. When the researchers blocked GDF15 in uveal melanoma cells, there were fewer, smaller liver tumors
The findings highlight GDF15 as a potential drug target for slowing or preventing eye cancer from spreading to the liver.
Q&A with Keiran Smalley, Ph.D., senior author and director of the Donald A. Adam Comprehensive Melanoma Research Center of Excellence at Moffitt.
What does this discovery mean for patients with uveal melanoma, both before the cancer possibly spreads to the liver and after it has spread?
Patients with class 2 uveal melanoma have a high risk of developing liver metastases. There are currently no FDA-approved strategies to prevent this from occurring. It is possible that early therapeutic targeting of GDF15 through anti-GDF15 antibodies could either delay or even prevent the outgrowth of liver metastases. In patients with established liver metastases, GDF15 could be required for the maintenance of liver metastases, but this would need to be tested through further studies.
Why does this type of eye cancer spread to the liver far more often than to other organs?
It is not clear why uveal melanoma has this unique preference for liver metastasis. Some studies have suggested that uveal melanoma cells can spread to multiple organs but only really grow in the liver.
Why did you focus on GDF15?
GDF15 is a signaling molecule that can be secreted by tumor cells and influence other tissues, making it a strong candidate for promoting communication between cancer cells and the liver. We focused on it because earlier research showed that uveal melanoma cells associated with liver metastases produce high levels of GDF15.
Could this discovery be used to develop new drugs or treatments to reduce or even prevent the spread of this form of eye cancer to the liver?
Antibodies that block the function of GDF15 have been shown to be highly effective at treating cancer cachexia, a condition that includes reduced desire to eat and weight and muscle loss. It is likely that these antibodies could be repurposed and evaluated as a therapy for uveal melanoma.
Can you envision this finding applying to other cancers?
Yes, GDF15 levels are known to be very high in colorectal carcinoma, renal cell carcinoma , lung cancer, and urothelial carcinoma. It is likely that GDF15 plays a similar role in these other cancers. If so, targeting GDF15 may offer new ways to target distant metastases.
This study was supported by the National Cancer Institute (R01CA256193; P30 CA076292; P30 CA247796; P30 CA142543), National Eye Institute (P30 EY030413), Cancer Prevention and Research Institute of Texas (RR220010), Research to Prevent Blindness, Inc., and appropriations from the State of Florida (Fla. Stat. § 381.915
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