"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!
Gene switch may repair DNA and prevent cancer
12.02.2016 | Institute for Integrated Cell-Material Sciences at Kyoto University
New method opens crystal clear views of biomolecules
11.02.2016 | Deutsches Elektronen-Synchrotron DESY
Today, plants and microorganisms are heavily used for the production of medicinal products. The production of biopharmaceuticals in plants, also referred to as “Molecular Pharming”, represents a continuously growing field of plant biotechnology. Preferred host organisms include yeast and crop plants, such as maize and potato – plants with high demands. With the help of a special algal strain, the research team of Prof. Ralph Bock at the Max Planck Institute of Molecular Plant Physiology in Potsdam strives to develop a more efficient and resource-saving system for the production of medicines and vaccines. They tested its practicality by synthesizing a component of a potential AIDS vaccine.
The use of plants and microorganisms to produce pharmaceuticals is nothing new. In 1982, bacteria were genetically modified to produce human insulin, a drug...
Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock which attains an accuracy which had only been predicted theoretically so far. Their optical ytterbium clock achieved a relative systematic measurement uncertainty of 3 E-18. The results have been published in the current issue of the scientific journal "Physical Review Letters".
Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock...
The University of Würzburg has two new space projects in the pipeline which are concerned with the observation of planets and autonomous fault correction aboard satellites. The German Federal Ministry of Economic Affairs and Energy funds the projects with around 1.6 million euros.
Detecting tornadoes that sweep across Mars. Discovering meteors that fall to Earth. Investigating strange lightning that flashes from Earth's atmosphere into...
Physicists from Saarland University and the ESPCI in Paris have shown how liquids on solid surfaces can be made to slide over the surface a bit like a bobsleigh on ice. The key is to apply a coating at the boundary between the liquid and the surface that induces the liquid to slip. This results in an increase in the average flow velocity of the liquid and its throughput. This was demonstrated by studying the behaviour of droplets on surfaces with different coatings as they evolved into the equilibrium state. The results could prove useful in optimizing industrial processes, such as the extrusion of plastics.
The study has been published in the respected academic journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).
Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels
A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...
12.02.2016 | Event News
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12.02.2016 | Physics and Astronomy
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12.02.2016 | Medical Engineering