Κυριακή, 22 Νοεμβρίου 2015

PROTEIN THAT INHIBITS PROSTATE CANCER METASTASIS

Scientists from Lawrence Livermore National Laboratory (LLNL), in collaboration with researchers from University of California Merced and Davis, have found that a secreted protein predominantly expressed in bone inhibits prostate cancer metastasis to bone. Their research was published recently by Hudson et al in PLOS ONE, and by Sebastian et al in Microarrays.
Bone tumors cause great pain, promote fractures, and ultimately represent the main cause of morbidity, with a 70% incidence documented by autopsies, according to Gabriela Loots, PhD, an LLNL biomedical scientist and Associate Adjunct Professor at UC Merced.
It has been hypothesized that the bone microenvironment serves as a rich “soil” by secreting factors that promote survival and propagation of cancer cells; in turn, tumors secrete factors that alter the bone microenvironment to promote metastatic colonization. Development of new therapies for the prevention and treatment of prostate cancer bone metastasis depends on understanding the dynamic reciprocal interactions between prostate cancer cells and the bone microenvironment.
Protein Identification
The first study identified the secreted bone protein sclerostin (SOST) as a key molecule dysregulated as a result of prostate cancer–bone microenvironment interactions.
This study, published in Microarrays, shows that lack of SOST in the bone microenvironment promotes the expression of many genes associated with cell migration and/or invasion, including long noncoding RNA MALAT1 in prostate cancer, suggesting that SOST has an inhibitory effect on prostate cancer invasion.
SOST Regulation
The second study looked into the role of SOST in regulating prostate cancer invasion and metastasis. Researchers found that SOST inhibits prostate cancer invasion in vitro. To determine whether SOST impacts metastasis in animals, they modified a prostate cancer cell line to overexpress SOST, engrafted various cells lines onto immunodeficient mice, and quantified the rate of secondary tumors and of osteolytic bone lesions. The researchers found that cells producing more SOST had significantly lower rates of metastasis. In addition, it was found that cells expressing more SOST induced significantly less osteolytic bone loss. These results provided strong evidence that SOST has an inhibitory effect on prostate cancer metastasis to bone.

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