"We then added cells from a mouse mammary tumor onto the replica bone," Malanchi said. "Most entered a dormant state, with only sporadic replication activity."

What did the inflammation experiment show?

Doctors already knew that bone injuries such as fractures can spur dormant metastatic cells to grow. The team wanted to test whether indirect, body-wide insults — such as injuries or infections far from the bone — could do the same.

The researchers induced intestinal colitis, which is inflammation in the gut, in mice carrying the replica bone with dormant metastatic cells. Because the engineered bone responds to the immune system, the gut inflammation triggered rapid production of immune cells from the bone marrow.

That remodeling of the marrow environment had a profound effect. More cancer cells started replicating, raising the risk of a tumor forming.

By analyzing which genes switched on in both bone cells and cancer cells, the team identified a key player: HMGB2, a molecule that stimulates cell growth. Its levels rose as immune cell production surged — and it also promoted the awakening of dormant cancer cells.

"Even without inflammation elsewhere in the body, just the increased HMGB2 in the artificial bone was enough to stimulate more cancer cells to activate," Malanchi said.

The team also examined bone samples from people with breast or prostate cancer. HMGB2 was present in areas where cancer cells were actively dividing.

What does this mean for patients in remission?

The results come with important caveats. The core experiments used a mouse model, not human patients, so the findings are preliminary in their clinical implications. Malanchi also cautions against reading the result as an all-or-nothing trigger.

"We think it's a piecemeal situation where each systemic change increases the chance of more metastatic cells waking up each time," she said.

Still, the study suggests a practical direction: monitoring people during the critical period after remission for infections, inflammation, or injury anywhere in the body could help indicate whether dormant cells are more likely to reactivate.

"Once cancer cells are actively replicating, they can respond to chemotherapy, so understanding developments affecting the bone marrow could lead to early intervention," Malanchi said.

In short, boosting immune cell production in the bone — a normal part of the body's response to inflammation — may come at a hidden cost: disrupting tumor dormancy and tipping the balance toward metastatic growth.

The study is published as: Stefania Di Blasio et al., "An extramedullary bone model of metastatic dormancy reveals an increased rate of metastatic reactivation upon distant insults," Cell Reports (2026). DOI: 10.1016/j.celrep.2026.118088.