A stem cell that helps to produce vertebrae also promotes the growth of tumors that migrate to the backbone from elsewhere.
Scientists have uncovered a novel type of stem cell that gives rise to the backbone — and which contributes to the common spread of breast tumors and other malignancies to the spine1.
Certain malignancies, including those of the breast, prostate, and lung, spread preferentially to the spine for unexplained reasons. Coughs, according to one 1940s idea, might temporarily reverse blood flow and shock cancer cells into the area of the spine, where they form new tumors.
According to Matthew Greenblatt, a pathologist at Weill Cornell Medicine in New York City and co-author of the new study, this is “still the classic dogma that’s taught in medical schools.” Greenblatt and his colleagues’ findings, he claims, “overturn this very old paradigm.”
Nature will publish the work on September 13th.
Developing a spine
Spines are unique to vertebrate animals, and the spinal vertebrae lack several of the proteins commonly associated with bones. These characteristics prompted Greenblatt and his colleagues to assume that they develop in a different way than other bones.
Breast cancer invasive cells on the hunt
Greenblatt’s research extracted stem cells from both the vertebrae and what are known as long bones, such as the femur in the leg, using mice. They discovered that stem cells from the two sites expressed significantly distinct sets of genes. The researchers implanted vertebral cells into the muscles of mice and discovered that the cells generated offspring that resembled the spectrum of cells present in the spine. They concluded from this and other evidence that they had discovered vertebral skeletal stem cells or vSSCs.
Greenblatt and colleagues “clearly and beautifully show” that vSSCs and long bone stem cells are “very, very different,” according to Noriaki Ono, a bone researcher at the University of Texas Health Science Center at Houston who provided mice for the work but was otherwise uninvolved in it.
Many scientists have previously “considered all the bones as the same organ,” according to cancer researcher Xiang Zhang of Baylor College of Medicine in Houston. “This research advances our understanding to a new level.”
The bad actor
The scientists’ discovery made them question if the new form of stem cell may explain some of the previously inexplicable patterns in cancer spread. The researchers focused on MFGE8, a protein released by vertebrate stem cells. In mouse tests, removing the gene for the protein reduced the likelihood of cancer cells spreading to the animals’ spines by around two-thirds.
The researchers isolated vSSCs from patients having spinal surgery and discovered that human vSSCs secreting MFGE8 were more likely to interact with cancer cells than non-secreting vSSCs. According to Ono, one protein cannot explain the entire phenomenon, but it appears to be a key component.
The consequences of the study may extend beyond cancer. According to research co-author Sravisht Iyer, a spinal surgeon at the Hospital for Special Surgery in New York City, spinal fusions — surgeries that fuse two or more vertebrae to ease pain from illnesses such as scoliosis and arthritis — frequently fail for unexplained reasons. He thinks that additional research into vSSCs will improve the success rate of these procedures.