The biology of brain colonization by metastatic cells
Spanish National Cancer Research Center (CNIO) Madrid, Spain
Existing evidences at the cellular, clinical and genomic levels suggest that brain metastases differ from their corresponding primary tumor. One reason that could underlie this divergent evolution might derive from the unique brain microenvironment.
An initial anti-metastatic naïve brain environment that eliminates the vast majority of recently extravasated cancer cells is slowly reprogrammed into a strong pro-tumor niche that finally supports the growth of the limited cells that survived. This switch from an anti-tumor to a pro-tumor brain microenvironment correlates with the emergence of altered molecular patterns affecting specific resident cell types. Specifically, we identified the activation of STAT3 pathway in reactive astrocytes surrounding brain metastasis. Genetic strategies demonstrated that this reprogrammed component of the microenvironment, which is not present in a normal brain, is responsible for establishing a potent immunomodulatory program that sustains the growth of brain metastasis through a network that involves macrophages and T cells.
The unprecedented success of a pharmacological strategy targeting this altered molecular pattern in reactive astrocytes from both mice and humans with brain metastasis suggests that current systemic approaches could be significantly improved by incorporating additional drugs targeting the microenvironment
Host: Juan M. Encinas