Why does cancer spread to the spine?

A widely accepted old theory from the 1940s of blood flow contributing to metastasis (cancer spreading) is now challenged by Cornell's team of scientists.

And it is not the blood flow- it is unique to spine line of stem cells.

The vertebral bones that form the spine are derived from a distinct type of stem cells. These stem cells secrete a protein that favors tumor metastases. Findings are reported by researchers at Weill Cornell Medicine.

The discovery opens up a new line of research on spinal disorders. It helps to explain why solid tumors so often spread to the spine. It could lead to new orthopedic and cancer treatments.

Researchers used bone-like “organoids” made from vertebral stem cells. They showed that the tendency of tumors to spread to the spine (more than to long bones such as leg bones)—is due to a special protein. This protein is called MFGE8, and it is secreted by these stem cells.

Study senior author, Dr. Matthew Greenblatt, an associate professor of pathology and laboratory medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and a pathologist at NewYork-Presbyterian/Weill Cornell Medical Center:

"We suspect that many bone diseases preferentially involving the spine are attributable to the distinct properties of vertebral bone stem cells."

Since vertebrae, in comparison with other bones such as arm and leg bones, develop along a different pathway early in life. They also appear to have had a distinct evolutionary trajectory. Dr. Greenblatt and his team hypothesized that a distinct vertebral stem cell probably exists.

The researchers started by isolating what is broadly known as skeletal stem cells. They give rise to all bone and cartilage. They form different bones in lab mice based on known surface protein markers of such cells.

They then analyzed gene activity in these cells. They wanted to see if they could find a distinct pattern for the ones associated with vertebral bone.

The first was a new and more accurate surface-marker-based definition of skeletal stem cells as a whole.

This new definition excluded a set of cells that were not stem cells that had been included in the old stem cell definition. This helped to simplify some prior research in this area.

They also found that skeletal stem cells from different bones vary in their gene activity.

From this analysis, the team identified a distinct set of markers for vertebral stem cells. They confirmed these cells form spinal bone in further experiments in mice and lab-dish cell culture systems.

The researchers next investigated the metastasis phenomenon. We know that of the spine’s relative attraction for tumor metastases. —including breast, prostate, and lung tumor metastases—compared to other types of bone.

The traditional theory, dating to the 1940s, coined the term-“spinal tropism”. This relates to patterns of blood flow that convey metastases to the spine versus long bones.

But when the researchers reproduced the spinal tropism phenomenon in animal models, they found evidence that blood flow isn’t the explanation. They found a clue pointing to vertebral stem cells as the possible culprits.

“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."

Said the study's first author Dr. Jun Sun, a postdoctoral researcher in the Greenblatt laboratory.

Subsequently, the Cornell team found that removing vertebral stem cells eliminated the difference in metastasis rates between spine bones and long bones.

Ultimately, they determined that MFGE8, a protein secreted in higher amounts by vertebral compared to long bone stem cells, is a major contributor to spinal tropism.

To confirm the relevance of the findings in humans, the team collaborated with investigators at the Hospital for Special Surgery to identify the human counterparts of the mouse vertebral stem cells and characterize their properties.

The researchers are now exploring methods for blocking MFGE8. This can help to reduce the risk of spinal metastasis in cancer patients.

Dr. Greenblatt's team is now studying how the distinctive properties of vertebral stem cells contribute to spinal disorders.

This article is written for educational purposes only. Please consult your naturopathic doctor for lifestyle changes that need to be implemented to decrease your chances of being diagnosed with cancer.

Here is a link to the original article:

https://news.weill.cornell.edu/news/2023/09/study-reveals-why-cancer-may-spread-to-the-spine?utm_source=join1440&utm_medium=email&utm_placement=newsletter

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