Targeting Cancer-Activated Stellate Cells Could Prevent Liver Metastasis

Recent research conducted by the University of the Basque Country highlights a groundbreaking approach to preventing liver metastasis by focusing on specific liver cells known as hepatic stellate cells (HSCs). Normally, HSCs play a crucial role in repairing liver damage by producing extracellular matrix components like collagen, leading to scar formation in response to injuries such as fibrosis or fatty liver. However, in the context of cancer, these cells can be co-opted to support tumor growth.

The study found that when metastatic tumors reach the liver, HSCs become activated and significantly contribute to tumor development. They do this by secreting collagen, promoting new blood vessel formation, and creating an environment that hampers immune defenses. Remarkably, experiments on mice demonstrated that removing these cancer-activated stellate cells almost entirely halted metastasis. This was achieved by reducing collagen buildup, blocking blood vessel formation, bolstering immune responses, and cutting off support for tumor progression.

Lead researcher Aitor Benedicto explained that the elimination of activated stellate cells curtailed metastasis, effectively dismantling the tumor’s microenvironment. This discovery opens new avenues for targeted therapies aimed at the tumor microenvironment, potentially transforming the treatment strategy for liver metastases.

The research also emphasizes that liver metastasis often originates from primary cancers such as colon, pancreatic, breast, or melanoma. The team is now investigating whether similar mechanisms are involved in metastasis driven by different primary tumors. Understanding how stellate cells are activated and identifying the key proteins involved could lead to new treatments that block metastasis at its early stages.

Given that approximately 70% of colon cancer patients develop liver metastases—often leading to death—the implications of this research are significant. Although further studies are needed, these findings represent a promising step toward therapies that could deactivate tumor-supporting liver cells, offering hope for more effective cancer treatments in the future.