Researchers at WashU Medicine have shown that cells originating in bone and best known for their role in bone formation are recruited to primary breast tumors, where they become cancer-associated fibroblasts, a type of cell that helps create the environment tumors need to grow.
The team, led by Roberta Faccio, a professor of orthopedics and a research member at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, found in human tissue samples that as much as 40% of cancer-associated fibroblasts expressed Osterix, a key marker of cells known as osteoblasts that regulate bone formation. The findings were published in Nature Communications.
Breast tumors appear to actively recruit bone cells for this task. These cells do not usually travel freely in the body, but a small number can be present in the bloodstream. Using mouse models, Faccio and her team found that breast tumors stimulate the release of cells from the bone marrow into the bloodstream, from where they infiltrate growing tumors. Like osteoblasts, the cells responsible for building bone, these tumor-infiltrating cells produce the extracellular connective structure that provides support to the tumor and surrounding tissue, and the specialized proteins that help create an environment that promotes tumor growth.
Additionally, the researchers identified a genetic signature in these bone-derived cells that is associated with poor breast cancer survival. Importantly, experiments targeting Osterix and another molecule called MMP13, both linked to the tumor-promoting activity of these bone-derived cancer-associated fibroblasts, reduced tumor growth. The findings suggest there may be a therapeutic benefit to targeting these bone-derived cells in breast tumors to slow disease progression and potentially improve patient outcomes.
