Newly discovered spine stem cells help explain cancer metastasis in bone
Researchers have found a particular type of stem cell that helps form the spine — and that secretes a protein that seems to attract cancer, which could help explain why certain types of cancer spread more often to the spine than to other bones.
The team, led by researchers at Weill Cornell Medicine and the Hospital for Special Surgery in New York, says the finding creates a research avenue that could lead to new orthopedic and cancer treatments.
Their study was published this month in the journal Nature. It shows that vertebral bone comes from a stem cell that is different from other stem cells that form bones. And it is a protein called MFGE8, which those stem cells secrete, which explains why cancer is more likely to spread to the spine than to long bones like the femur.
“We suspect that many bone diseases preferentially involving the spine are attributable to the distinct properties of vertebral bone stem cells,” study senior author Dr. Matthew Greenblatt, associate professor of pathology and laboratory medicine at Weill Cornell Medicine and a pathologist at New York-Presbyterian/Weill Cornell Medical Center, said in a news release.
The Washington Post explains stem cells as “the body’s raw materials. They can divide and form more stem cells, or develop to reach a more specific destiny as skin, red blood cells, neurons or any of the estimated 200 different cell types in the human body.”
Past research has shown types of bone come from their own specialized bone stem cells. Because vertebrae develop differently and early in life, they suspected there is a “distinct” vertebral stem cell.
Using protein markers in mice on skeletal stem cells, they looked at those cells for a pattern linked to vertebral bone. Their methods led to finding “a new and more accurate surface-marker-based definition of skeletal stem cells,” discounting cells that had been included but turned out not to be stem cells. Researchers also discovered that skeletal stem cells from different bones do not have the same genetic cell activity.
Using different experiments in mice and lab dish cultures, they confirmed that certain identified cells form spinal bone.
From there, they examined how breast, prostate and lung tumors metastasize to the spine, compared to other types of bone. Their work debunks the decades-old theory that it is blood flow that sends tumors to the spine more often than to other bones.
“We observed that the site of initial seeding of metastatic tumor cells was predominantly in an area of marrow where vertebral stem cells and their progeny cells would be located,” first author Dr. Jun Sun, a postdoctoral researcher in Greenblatt’s laboratory, said.
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When they removed the vertebral stem cells, cancer was as likely to spread to other bones as to the spine. The difference, they found, was MFGE8 secreted at a higher rate by vertebral stem cells compared to other bone stem cells.
The researchers said they’re looking for ways to block the protein to reduce risk of spinal metastasis in cancer patients. And they are studying how the properties of the vertebral stem cells are linked to spinal disorders.
“There’s a subdiscipline in orthopedics called spinal orthopedics and we think that most of the conditions in that clinical category have to do with this stem cell we’ve just identified,” Greenblatt said in the prepared statement.
Per The Washington Post, “In separate work, Greenblatt and his co-author on the Nature paper, Sravisht Iyer, a spine surgeon at the Hospital for Special Surgery, are investigating the role the new stem cell plays in responding to spine fusion surgery. They want to determine whether an implant of the new stem cell at the time of surgery can improve fusion.”
