CCN3/Nephroblastoma Overexpressed Is a Functional Mediator of Prostate Cancer Bone Metastasis That Is Associated with Poor Patient Prognosis
| Autor: | Estelle Schmitt, Laudine Communal, Fred Saad, Anne-Marie Mes-Masson, Véronique Barrès, Dru Perkins, Christine Caron, Veronique Ouellet, Matthew Dankner, Peter M. Siegel, Matthew G. Annis |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Context (language use) Bone Neoplasms Pathology and Forensic Medicine Metastasis 03 medical and health sciences Prostate cancer Nephroblastoma Overexpressed Protein 0302 clinical medicine Mediator Cell Line Tumor medicine Humans Neoplasm Metastasis Tissue microarray integumentary system business.industry Bone metastasis Prostatic Neoplasms Prostate-Specific Antigen medicine.disease Neoplasm Proteins Androgen receptor Gene Expression Regulation Neoplastic 030104 developmental biology Receptors Androgen 030220 oncology & carcinogenesis Cancer research Biomarker (medicine) Kallikreins business Signal Transduction |
| Zdroj: | The American journal of pathology. 189(7) |
| ISSN: | 1525-2191 |
| Popis: | Prostate cancer (PC) commonly metastasizes to the bone, resulting in pathologic fractures and poor prognosis. CCN3/nephroblastoma overexpressed is a secreted protein with a known role in promoting breast cancer metastasis to bone. However, in PC, CCN3 has been ascribed conflicting roles; some studies suggest that CCN3 promotes PC metastasis, whereas others argue a tumor suppressor role for CCN3 in this disease. Indeed, in the latter context, CCN3 has been shown to sequester the androgen receptor (AR) and suppress AR signaling. In the present study, we demonstrate that CCN3 functions as a bone-metastatic mediator, which is dependent on its C-terminal domain for this function. Analysis of tissue microarrays comprising >1500 primary PC patient radical prostatectomy specimens reveals that CCN3 expression correlates with aggressive disease and is negatively correlated with the expression of prostate-specific antigen, a marker of AR signaling. Together, these findings point to CCN3 as a biomarker to predict PC aggressiveness while providing clarity on its role as a functional mediator of PC bone metastasis. |
| Databáze: | OpenAIRE |
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