"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!
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The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
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Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.
K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...
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