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Molecule Linked to Reawakened Prostate-Cancer Cells

Dormant prostate-cancer cells in bone tissue can be reawakened, causing the disease to spread to different parts of the body.

The discovery, by researchers in the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, in Los Angeles, could lead to new ways to intervene before the disease progresses.

"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 lead study authorChia-Yi "Gina" Chu, PhD, a researcher and postdoctoral fellow in the Uro-Oncology Research Program. The findings were published in the journal Endocrine-Related Cancer.

The cells’ reawakening was caused by RANKL, a molecule produced by inflammatory cells. The researchers genetically engineered the cells to produce an excessive amount of RANKL and discovered those cells could cause surrounding dormant cells to change into aggressive cancer cells.

But tumors failed to form when researchers blocked the RANKL cells and their targets.

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.

The study was conducted with mice, but researchers said they planned to work toward human studies.

"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.

 

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