“Cancer has this uncanny ability to turn other cell types it comes in contact with to the cancer cell’s advantage,” explained Karen Bussard, the study's senior author and a researcher at the Sidney Kimmel Cancer Center - Jefferson Health. “For example, cancer cells can turn the immune cells that should kill it, into its own guards. However, we have now found a population of bone cells that not only resists, but subdues the cancer. It’s fascinating.”
Bussard and her team looked at what happens to bone cells once they interact with breast cancer cells that have migrated to the bones. For their study, they searched the tumor-bearing tibia of mice for osteoblasts – bone cells responsible for repair and the synthesis of new bone. They also examined tissue from patients with bone metastatic breast cancer for the presence of osteoblast subpopulations. (Related: Popular bone drugs double cancer risk.)
The team discovered that osteoblasts from both mice and humans changed after they interacted with bone-metastatic breast cancer cells. But instead of being co-opted by cancer cells to promote cancer metastasis -- as earlier studies have reported -- the osteoblasts stopped doing their normal functions and began producing factors that could halt cancer cell growth. The researchers observed this effect on estrogen receptor-positive breast cancer cells and in triple-negative breast cancer cells, one of the most aggressive types of breast cancer cells.
According to a previous study published in Science and Medicine, the osteoblasts of patients with advanced stage bone-metastatic breast cancer stop functioning. This causes a loss in bone density, a symptom common in patients with this type of cancer. But Bussard and her team discovered that in the earlier stages of the disease, osteoblasts are more resilient toward cancer cells that enter the bone. Upon interacting with cancer cells, these bone cells quickly adapt and release factors that put these invaders in stasis.
The molecules produced by osteoblasts change the behavior of cancer cells by restoring the production of the cell-cycle checkpoint protein p21, which stops cancer cells from proliferating. The researchers noted, however, that only osteoblasts that came into contact with metastatic breast cancer cells developed the ability to slow cancer cell growth.
“The bone-building osteoblast cells have a complex relationship with cancer,” said Bussard. “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 [the] 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.”
Researchers have long been interested in finding out how how breast cancer cells prosper through metastasis to the bone. According to Karen Knudsen, the director of Sidney Kimmel Cancer Center - Jefferson Health, Bussard and her team's breakthrough discoveries pave the way toward developing new strategies to prevent or treat metastatic cancers.
The researchers are now planning to learn more about the molecules that osteoblasts use to suppress cancer growth to better understand how they can be used to keep cancer cells dormant forever.