Researchers at Cornell University have identified a protein called MFGE8 secreted by spinal bone progenitor stem cells that appears to drive metastasis to the spine. This finding helps explain why cancer cells frequently colonize vertebral sites and opens the door to new strategies that specifically target MFGE8 to curb spinal metastases. The study appears in Nature.
Earlier work showed that bones originate from distinct stem cell populations, with vertebral bones emerging from a specialized lineage that produces MFGE8. Building on these observations, the researchers demonstrated that MFGE8 not only supports bone formation but also facilitates the spread of malignant tumor cells to the spine. This dual role helps connect vertebral biology with metastatic tropism and offers a concrete molecular mechanism for why spinal metastasis occurs more often in some cancer patients.
Historically, scientists have debated why the spine is at higher risk for metastatic seeding. A long-standing theory suggested that the distribution of blood flow—patterns thought to funnel circulating tumor cells toward the spine—was responsible. However, this vascular-centric explanation has not been definitively confirmed. The current work shifts attention toward the cellular environment of the spine itself, proposing that the vertebral stem cell population and its MFGE8 output create a receptive niche for metastasis.
In functional experiments, removing or inhibiting the vertebral stem cell activity reduced the spine’s attractiveness to metastatic cells. This indicates that vertebral progenitors actively shape the microenvironment in a way that promotes cancer spread. Parallel work in human tissues has identified counterparts to the mouse vertebral stem cells, enabling researchers to test whether MFGE8 plays the same role in people. The team is pursuing approaches to block MFGE8 signaling with the aim of lowering spinal metastatic risk in cancer patients.
The implications extend beyond spine-specific disease. MFGE8 is thought to influence cell adhesion and communication in bone and other tissues, suggesting that this protein could be a broader regulator of metastatic pathways. By dissecting how vertebral stem cells control MFGE8 production and how this protein interacts with circulating tumor cells, scientists hope to uncover new intervention points that prevent or slow metastasis at its earliest stages. The work underscores how tissue-specific stem cells can shape cancer biology and identifies a tangible target for therapeutic development.
These findings complement ongoing efforts to map the cellular and molecular landscape of metastasis. While more studies are needed to translate these discoveries into approved therapies, the research provides a clear rationale for pursuing MFGE8 inhibitors or related strategies as part of combination treatments. If successful, such approaches could reduce spinal metastasis, improve quality of life for patients, and extend survival by limiting the spread of cancer to the spine. The study emphasizes a shift toward targeting the tumour microenvironment in addition to tumor cells themselves, highlighting the intricate interplay between stem cell biology and cancer progression (Nature).