In breast cancer, there are cases of women and men whose cancer returns in their bones 20-30 years after they were treated for their primary disease and thought they were cancer-free. What was happening in bones that allowed the cancer cells to remain there for up to 30 years; alive but in a sleeping state, only to re-awaken decades later? In a step towards answering these questions, Dr. Bussard recently discovered a type of bone cell that can subdue cancer cells; slowing their growth, even in one of the most aggressive types of breast cancer.
Together with co-first authors and graduate students, Alexus D. Kolb and Alison B. Shupp and others, Dr. Bussard probed how bone cells change once they interact with breast cancer cells in the bone. Specifically, they looked at osteoblasts a kind of bone cell that lays down new bone; like cement, during growth and repair. The research team showed that the osteoblast cells from mice as well as humans drastically changed their function; after interacting with bone-metastatic breast cancer cells.
Earlier studies had shown that in advanced stage bone-metastatic breast cancer patients; osteoblasts stopped working; failing to produce a matrix that stabilizes and strengthens the bone. The changes lead to loss of bone density that is common in these patients. In her new work, Dr. Bussard and colleagues showed that in earlier stages of the disease, when cancer cells first enter the bone, rather than producing new bone; osteoblasts may divert their energy toward producing factors to halt cancer cell growth.
Receptor positive breast cancer
When osteoblasts from humans or mice were exposed to triple negative or estrogen receptor positive breast cancer cells that had migrated to the bone, the osteoblasts released factors that changed cancer cell behavior. These factors were able to swing the balance away from limitless cancer cell growth, and toward restoring production of the cell-cycle checkpoint protein p21, which stops metastatic breast cancer cells from replicating endlessly.
“The bone-building osteoblast cells have a complex relationship with cancer. “In advanced stages of the disease, we know that metastatic breast cancer cells can co-opt the normal cells of the bone to help cancer metastases thrive. However, our new work suggests that during early stages of the disease, such as when metastatic breast cancer cells first migrate to the bone, these cancer-exposed osteoblasts resist and fight cancer growth.”
“Understanding how breast cancer cells prosper through metastasis to bone has been a long-held goal of the breast cancer research community. Dr. Bussard’s breakthrough discoveries pave the way toward developing new strategies to prevent or treat metastatic disease. Is to fully characterize the molecules that osteoblasts use to reign in cancer growth, and see whether it’s possible to turn that understanding toward treatments that can put cancer cells to sleep forever.