A recent investigation led by scientists at Weill Cornell Medicine has shown that vertebral bones in the spine are produced from a specialized type of stem cell. This stem cell emits a protein known as MFGE8, which is instrumental in the spread of tumors. This significant revelation offers new perspectives into why tumors frequently localize in the spine, as well as the potential for groundbreaking therapies in both orthopedics and cancer treatment.
According to the study published on September 13 in the journal Nature, the researchers established that the spinal vertebrae come from a stem cell variant unlike those responsible for other bones. By creating organoids resembling bone from these unique vertebral stem cells, they demonstrated that the protein MFGE8 plays a significant role in the proclivity of tumors to migrate to the spinal region rather than to longer bones like those in legs.
Dr. Matthew Greenblatt, the study’s senior author and an associate professor of pathology and laboratory medicine, affiliated with both the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, remarked that this particular type of stem cell could be at the root of many bone diseases that primarily affect the spine.
In recent years, various researchers including Dr. Greenblatt have discovered that distinct stem cells give rise to different types of bones. Given that vertebral bones develop differently and have followed a separate evolutionary path compared to other bones like those in arms and legs, the team hypothesized the existence of a unique vertebral stem cell.
To test this hypothesis, the researchers began by isolating what are broadly categorized as skeletal stem cells, which are the precursors of all bones and cartilage, from diverse bones in lab mice. They then conducted gene activity analyses on these cells, and discovered a unique genetic signature associated with vertebral stem cells.
Two crucial findings emerged from this effort. The first was a more precise definition for skeletal stem cells based on surface markers, which clarified some ambiguities in earlier research. The second was the identification of a distinct gene activity pattern in vertebral stem cells, which was subsequently confirmed through further experiments involving mice and cell cultures.
To understand why tumors preferentially metastasize to the spine rather than other bones, the researchers abandoned a traditional theory dating back to the 1940s that attributed this behavior to blood flow patterns. When they replicated the spinal preference for tumor spread in animal models, their results suggested that blood flow was not the main factor; rather, vertebral stem cells appeared to play a critical role.
Dr. Jun Sun, the study’s first author and a postdoctoral researcher in the Greenblatt laboratory, noted that the initial implantation of metastatic tumor cells predominantly occurred where vertebral stem cells and their progeny are usually located.
The team also found that the removal of these specialized stem cells eliminated the disparity in metastasis rates between spinal and long bones. They concluded that the protein MFGE8, secreted in higher concentrations by vertebral stem cells, is a significant driver of the tendency for tumors to spread to the spine.
To validate their discoveries, the researchers collaborated with experts at the Hospital for Special Surgery to identify and examine the human equivalents of these mouse vertebral stem cells.
Ongoing research is now focused on methods to inhibit MFGE8 to minimize the risk of spinal metastasis in cancer patients. Moreover, Dr. Greenblatt mentioned that they are examining how the unique features of these vertebral stem cells may be connected to various spinal disorders.
Reference: “A vertebral skeletal stem cell lineage driving metastasis” by Jun Sun et al., 13 September 2023, Nature.
DOI: 10.1038/s41586-023-06519-1
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Frequently Asked Questions (FAQs) about Spinal metastasis in cancer research
What is the main focus of the Weill Cornell Medicine study?
The main focus of the study is to understand why tumors often metastasize to the spine. Researchers discovered that a unique type of stem cell in the spinal vertebrae secretes a protein called MFGE8, which promotes tumor metastasis.
Who led the study and where was it published?
The study was led by Dr. Matthew Greenblatt, an associate professor of pathology and laboratory medicine at Weill Cornell Medicine. The findings were published in the journal Nature on September 13, 2023.
What is the significance of the protein MFGE8?
The protein MFGE8 is secreted by a unique type of stem cell in the spinal vertebrae and is found to be instrumental in promoting the metastasis of tumors to the spine.
How could this research impact the field of oncology?
The findings offer a new line of investigation into why tumors frequently spread to the spine. This could pave the way for developing new treatments aimed at blocking the protein MFGE8 to minimize the risk of spinal metastasis in cancer patients.
Could the research also have implications for orthopedic treatments?
Yes, the research provides new insights into spinal disorders and paves the way for potential new treatments in orthopedics. The unique stem cells in the spinal vertebrae may be linked to various conditions that primarily affect the spine.
What animal models were used in the study?
The researchers used lab mice to isolate what are broadly categorized as skeletal stem cells. They conducted gene activity analyses on these cells to identify the unique stem cells responsible for forming spinal vertebrae.
What is the next step in this research?
The researchers are exploring methods to inhibit the protein MFGE8 to reduce the risk of spinal metastasis in cancer patients. They are also investigating how these unique stem cells might be involved in various spinal disorders.
Was the study collaborated with any other institutions?
Yes, to validate their discoveries, the researchers collaborated with experts at the Hospital for Special Surgery to identify and examine the human equivalents of these mouse vertebral stem cells.
More about Spinal metastasis in cancer research
- Weill Cornell Medicine
- Nature Journal
- Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine
- NewYork-Presbyterian/Weill Cornell Medical Center
- Hospital for Special Surgery
- DOI for the Study
