The spread of bone metastases is related to bone remodeling

Years to decades after breast tumor removal, the tumor may recur or metastasize to other organs
.
Bones are often affected by metastasis, and in a recent study published in the journal Cancer Discovery, a team led by researchers at Baylor College of Medicine showed in animal models that the onset of bone metastases is combined with
normal bone repair processes.
These findings provide a new direction
for future research on the prevention of tumor recurrence.

Corresponding author Xiang H.
-F.
"As cancer progresses, some cells may leave the primary tumor and metastasize to bone, but we still don't fully understand what determines the fate of these cells — what we call metastatic seeds
," Zhang said.

Zhang explained that many metastatic seeds will die, while others may remain inactive and patients will be asymptomatic
after the primary tumor is removed.
"But in a significant number of patients, the cancer recurs after a period of time," said Dan M.
, professor of molecular and cell biology, McNair Scholar, and Baylor University.
Zhang said, a
member of the Dan L Duncan Comprehensive Cancer Center.

Research has begun to uncover events
that may trigger dormant metastatic seed arousals.
Previously, Zhang and his colleagues observed that metastatic seeds tend to concentrate where
osteoblasts are.
Osteoblasts are responsible for the process of
forming new bone.

Bones are a very active organ
.
It is being transformed
every day.
If a fracture occurs, the process is more dramatic
.
The injured bone is broken down and new bones grow to repair the damage
.

"Seeing that the metastatic seeds were located next to osteoblasts, we wondered if there was a relationship
between bone metastasis and bone repair," Zhang said.

On a mouse model, the team investigated the effects of
triggering the bone repair process on bone metastasis.
They found that activating this process led to significantly more transfers
.
In addition, they found a subset of bone stem cells expressing the marker NG2, called NG2-positive (NG2+) cells
.
These cells, long thought to drive normal bone turnover, appear to be directly involved in the awakening
of metastatic seeds.
The researchers showed that when they removed the NG2 marker from the gene from these cells, there were fewer
metastases.

"Until bone repair is triggered, such as injury, two cell types, NG2+ and cancer cells
, are dormant.
But when the bone needs to be repaired, there is a signal that triggers the conversion
of the bone.
”

NG2+ stem cells sense this signal and respond
by migrating to the place where bone needs to be rebuilt and differentiating into cells for repair.
"Interestingly, we found that cancer cells can physically adhere to NG2+ cells through cell adhesion molecules," Zhang said
.

These findings suggest that cancer cells may "ride" NG2+ cells, which will take them to remodeling sites, where, using differentiation and migration processes, they may shift from dormant cancer cells to active dividing cancer cells, creating new tumors
.

Zhang said: "This study opens up new ideas
on how to prevent bone metastasis.
Cancer cells are already present in bones, but interfering with their connection to NG2+ cells may one day help stop or control bone metastasis
.
”

Bone metastasis initiation is coupled with bone remodeling through osteogenic differentiation of NG2+ cells