Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical outcomes for high-risk neuroblastoma patients remains poor, with only 40-50% 5-Year overall survival (OS) and <10% long-term survival. The ongoing acquisition of genetic/molecular rearrangements in undifferentiated neural crest cells may endorse neuroblastoma progression. This study recognized the loss of Retinal Degeneration protein 3, RD3 in aggressive neuroblastoma, and identified its influence in better clinical outcomes and defined its novel metastasis suppressor function. The results showed ubiquitous expression of RD3 in healthy tissues, complete-loss and significant TNM-stage association of RD3 in clinical samples. RD3-loss was intrinsically associated with reduced OS, abridged relapse-free survival, aggressive stage etc., in neuroblastoma patient cohorts. RD3 was transcriptionally and translationally regulated in metastatic site-derived aggressive (MSDAC) cells (regardless of CSC status) ex vivo and in tumor manifolds from metastatic sites in reproducible aggressive disease models in vivo. Re-expressing RD3 in MSDACs reverted their metastatic potential both in vitro and in vivo. Conversely muting RD3 in neuroblastoma cells not only heightened invasion/migration but also dictated aggressive disease with metastasis. These results demonstrate the loss of RD3 in high-risk neuroblastoma, its novel, thus-far unrecognized metastasis suppressor function and further imply that RD3-loss may directly relate to tumor aggressiveness and poor clinical outcomes.
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PMID:RD3 loss dictates high-risk aggressive neuroblastoma and poor clinical outcomes. 2637 49

The 195-amino-acid-long human Retinal Degeneration Protein 3 (RD3) is critical in the regulation of guanylate cyclase (GC) signaling and photoreceptor cell survival. Recently, we identified significant loss of RD3 in high-risk neuroblastoma and the influential role of RD3 in tumor progression. However, the functional characterization of RD3 in tumor systems has been hampered by the dearth of information on its localization in normal tissue and by the lack of antibodies suitable for staining FFPE tissue, primarily due to the inaccessibility of the epitopes. In this study, we validated a custom-synthesized RD3 antibody and investigated the expression/localization of RD3 in assorted human tissues. We observed stratified expression of RD3 in different cell types and subcellular location of retina. We demonstrated extensive positive RD3 immunoreactivity in various normal tissues and particularly strong dot-like perinuclear staining in the lining epithelial cells, suggesting that RD3 may play an important role in the normal functioning of epithelial cells. RD3 expression is limited in the CNS. While neuroblastoma is often RD3-positive, the adrenal medulla, where many neuroblastomas originate, is RD3-negative. Meta-analysis of RD3 transcriptional expression across normal tissues confirmed tissue-specific RD3 mRNA levels. Our results revealed the tissue-specific expression/localization profile of RD3 for the first time.
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PMID:Retinal Degeneration Protein 3 (RD3) in normal human tissues: Novel insights. 2903 Jun 14