Researchers have developed a new method to study how cancer cells hijack normal cells during metastasis, revealing a surprising role for estrogen receptors in bone tumors—even in male patients.
New Technique Reveals the "Neighborhood" of Metastasis
Scientists at Baylor College of Medicine and collaborating institutions have created a method called Sortase A–Based Microenvironment Niche Tagging (SAMENT). This technique allows researchers to specifically label normal cells that are in direct contact with cancer cells during the process of metastasis. Published in Cell, the study used SAMENT to identify shared features of the "metastatic niche" across several cancer models.
A key finding was an abundance of macrophages and a scarcity of immune-activating T cells in these tumor-friendly microenvironments.
A Hormonal Switch in Immune Cells
A surprise emerged when examining bone metastases. The researchers found unexpected activation of estrogen receptor alpha (ERα) in macrophages—immune cells that usually help fight disease. This activation was not seen in normal bone tissue or in primary tumors.
"ERα-active macrophages were also found in human bone metastasis samples from breast, lung, and kidney cancers, including male patients."
How Cancer Cells Manipulate Macrophages
The study traced how this happens. Cancer cells deliver fatty acids to macrophages, likely via tiny packets called extracellular vesicles. This fatty acid delivery activates a metabolic pathway that turns on ERα signaling in the macrophages.
Active ERα makes macrophages immunosuppressive, effectively blocking T cells from reaching and killing the tumor cells.
Proof in Mouse Models
In experiments with mice, genetic removal of ERα from macrophages reduced cancer cell colonization of bone, slowed tumor growth, and decreased metastasis to other organs—all without affecting normal bone health.
A Potential Drug Repurposing
This discovery points to an existing treatment. Fulvestrant, an FDA-approved drug that degrades estrogen receptors, allowed T cells to enter bone metastatic lesions and kill tumor cells in the mouse models.
The authors suggest that further clinical trials are warranted to evaluate estrogen-blocking therapies for bone metastases across multiple cancer types in both women and men.