Newly discovered stem cells provide clues to the mystery of cancer

Newly discovered stem cells provide clues to the mystery of cancer

Scientists have discovered a new type of stem cell in the spine that appears crucial to solving a long-standing mystery: why so many more cancer cells spread to the spine than to other bones in the body.

When breast, lung and prostate cancers spread to multiple bones in the body, the cancer is three to five times more likely to reach the spine than in the lower and upper extremities. Scientists have known about this disparity for decades, but its cause has remained unclear.

One theory held that differences in blood flow may be the cause. But the new findings suggest an alternative that could have implications for cancer care, spinal fusion surgery, and osteoporosis, a bone-weakening disease that affects about 10 million Americans.

Stem cells are like the body’s raw materials. They can divide and form more stem cells, or develop to reach a more specific fate such as skin, red blood cells, nerve cells, or any of the estimated 200 different cell types in the human body.

In the journal Nature, researchers from Weill Cornell Medical College and the Hospital for Special Surgery in New York report the discovery of what they call vertebral skeletal stem cells in the spine. These cells make a protein that acts as a “come hither” signal to cancer cells, a discovery that raises new therapeutic possibilities.

“We expect this discovery to target these cells to disrupt their function and ultimately reduce the spread of cancer to the spine,” said Matthew P. Greenblatt, one of the study’s authors and a pathologist at Weill Cornell Medical College.

In work spanning five years, scientists discovered the cells first in mice, then in humans. Cells responsible for bone formation appear in the vertebrae with osteosclerosis.

To demonstrate the critical role of vertebral skeletal stem cells, the researchers developed a mouse from which they could truncate some of its DNA. Using an enzyme, they removed a gene specific for bone formation from the newly discovered vertebral stem cells. Mice in which the gene was removed showed pronounced spinal defects, proving the importance of new stem cells in spine formation.

The scientists then transplanted the stem cells into a mouse’s leg muscle. The transplanted cells created new miniature bones from scratch and produced all types of skeletal cells found in the spine. The researchers concluded that vertebral skeletal stem cells help form the spine before birth, and then help maintain it after birth.

To find the same stem cells in humans, researchers studied very small pieces of vertebrae removed during laminectomies, surgeries that relieve pressure on the nerves and spinal cord.

“It’s very rare to find a new stem cell, and that’s one of the things that makes us excited about this,” Greenblatt said. “We think there is more to discover.”

By comparing the stem cells that make up spinal bone with those that make up limb bones, they discovered one protein that is made at much higher levels in the vertebrae. Mice lacking this protein saw much less spread of cancer into the spine.

Vinnie Zhu, a core faculty member at the University of Washington’s Institute for Stem Cell and Regenerative Medicine, called the study “a breakthrough that helps us understand the evolutionary origin of vertebrae.” Zhou, who was not involved in the project, added that the research “may help us understand ways to be more creative” in slowing or stopping spinal metastasis.

Sean Morrison, founding director of the Children’s Research Institute at the University of Texas Southwestern Medical Center in Dallas, said he considers the cells the researchers described to be skeletal stem cells, a type whose existence has been known for years.

but Morrison, who is also a researcher at the Howard Hughes Medical Institute, added that the paper still shows that skeletal stem cells found in different parts of the body have somewhat different properties.

“Skeletal stem cells in the vertebrae have an amazing ability to attract cancer cells that you don’t see in other skeletal stem cells,” he said.

Rory Goodwin, MD, a neurosurgeon and spine surgeon at Duke Health, praised the paper’s authors and said the stem cell discovery may help researchers improve the poor outlook for cancer patients whose disease has spread to the spine.

“When patients have a spinal metastasis, it’s usually at the end of the line,” Goodwin said. He added that the average survival is between 10 and 14 months once the cancer reaches the spine, “with some patients surviving much less than that.”

In addition, this finding provides an explanation for why osteoporosis is so different in the spine compared to other parts of the skeleton. This knowledge can help doctors design treatment for the disease when it appears in the spine.

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 that new stem cells play in the response to spinal fusion surgery. They want to determine whether transplanting new stem cells at the time of surgery can improve fusion.

The two scientists also suspect the possibility of a second type of vertebral skeletal stem cell. When they blocked the new stem cell’s ability to form bone, they found small amounts of bone in some areas of the spine, raising the question of whether a second stem cell type might be responsible.

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