Dormant Prostate Cancer Cells May Be Reawakened by Factors Produced in Inflammatory Cells

In a recent study conducted by researchers in the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, it was found that dormant prostate cancer cells in bone tissue can get reawakened causing metastasis to other parts of the body. Understanding of this mechanism will help researchers to intervene before disease progression.   

"Understanding how and why dormant cells in bone tissue metastasize will aid us in preventing the spread of disease, prolonging survival and improving overall quality of life," said Chia-Yi "Gina" Chu, PhD, a researcher and postdoctoral fellow in the Uro-Oncology Research Program and lead author of the study published in the journal Endocrine-Related Cancer.

The researchers conducting the study found that exposure to RANKL triggered the reawakening of cancerous cells in the bone. RANKL is a signalling molecule commonly produced by inflammatory cells. Researchers genetically engineered cells to overproduce RANKL. They found in lab studies and in laboratory mice that these cells were equipped to significantly  alter the gene expression of surrounding dormant cells so that they transformed into aggressive cancerous cells. 

When researchers injected these genetically engineered RANKL cells directly into the blood circulation of laboratory mice, it caused dormant cells within the skeleton to reawaken, creating tumors within the bone. When the RANKL receptor or its downstream targets were blocked, tumors did not form.

"After examination, these engineered tumors were found to contain both RANKL-producing prostate cancer cells and dormant cells, which had been transformed to become cancerous," said Chu. "However, the transformed cells displayed aggressive traits that would metastasize to bone and become resistant to standard hormone therapies used to treat the disease."

Though findings are preliminary, researchers plan to identify other cells known to produce RANKL that may also recruit and reprogram dormant cells to colonize bone tissue. Investigators plan to embark into clinical research with human patients in collaboration with leading Cedars-Sinai researchers, including Edwin Posadas, MD, medical director of the Urologic Oncology Program.

"Though more work must be done to understand how RANKL reprograms dormant cells to become cancerous, we look forward to examining its influence on promoting metastasis and secondary tumors, as well as the possibility of 'deprogramming' metastatic cancer cells," said Leland Chung, PhD, director of the Uro-Oncology Research Program.