"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.
In the study, investigators found that cancerous cells in the bone were reawakened after exposure to RANKL, a signaling molecule commonly produced by inflammatory cells. Researchers then genetically engineered cells to overproduce RANKL and found that these cells could significantly alter the gene expression of surrounding dormant cells in lab studies and in laboratory mice, causing them to transform into aggressive cancer cells.
Researchers then injected these engineered RANKL cells directly into the blood circulation of laboratory mice, which 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.
Cedars-Sinai collaborators include Michael Freeman, PhD, director of cancer biology and therapeutics in the Department of Biomedical Sciences and vice chair in the Department of Surgery; Haiyen E. Zhau, PhD, professor in the Department of Medicine; Ruoxiang Wang, PhD, associate professor in the Department of Medicine; Andre Rogatko, PhD, director of the Biostatistics and Bioinformatics Core; and Sungyong You, PhD, and Jayoung Kim, PhD, both researchers in the Department of Surgery.
Xu Feng, PhD, and Majd Zayzafoon, MD, PhD, from the University of Alabama, Birmingham; Mary C. Farach-Carson, PhD, from Rice University; and Youhua Liu, PhD, from the University of Pittsburgh, contributed to the study.
This research is supported in part by grants from National Cancer Institute (P01-CA098912, R01-CA122602), the Prostate Cancer Foundation, including both a Challenge Award and a Young Investigator Award, and Cedars-Sinai Medical Center Board of Governors Endowed Chair in Cancer Research.
Citation: Endocrine-Related Cancer. 2014 January: RANK- and c-Met-mediated signal network promotes prostate cancer metastatic colonization.
Cara Martinez | EurekAlert!
Shark Tagged by NSU’s Guy Harvey Research Institute Is Apparently Enjoying Time in Warm, Tropical Waters
30.03.2015 | Nova Southeastern University
Misuse of Sustainability Concept May Lead to Even More Toxic Chemical Materials
30.03.2015 | Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
30.03.2015 | Press release
30.03.2015 | Life Sciences
30.03.2015 | Earth Sciences