"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!
Severity of enzyme deficiency central to favism
26.07.2016 | Universität Zürich
From vision to hand action
26.07.2016 | Deutsches Primatenzentrum GmbH - Leibniz-Institut für Primatenforschung
Transparent electronics devices are present in today’s thin film displays, solar cells, and touchscreens. The future will bring flexible versions of such devices. Their production requires printable materials that are transparent and remain highly conductive even when deformed. Researchers at INM – Leibniz Institute for New Materials have combined a new self-assembling nano ink with an imprint process to create flexible conductive grids with a resolution below one micrometer.
To print the grids, an ink of gold nanowires is applied to a substrate. A structured stamp is pressed on the substrate and forces the ink into a pattern. “The...
A new Fraunhofer MEVIS method conveys medical interrelationships quickly and intuitively with innovative visualization technology
On the monitor, a brain spins slowly and can be examined from every angle. Suddenly, some sections start glowing, first on the side and then the entire back of...
Researchers at the U.S. Department of Energy's (DOE) Ames Laboratory have discovered an unusual property of purple bronze that may point to new ways to achieve high temperature superconductivity.
While studying purple bronze, a molybdenum oxide, researchers discovered an unconventional charge density wave on its surface.
Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.
Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...
Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases
Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...
15.07.2016 | Event News
15.07.2016 | Event News
11.07.2016 | Event News
26.07.2016 | Information Technology
26.07.2016 | Health and Medicine
26.07.2016 | Physics and Astronomy