The Role of Interleukin-6/GP130 Signaling in Prostate Cancer Progression and Its Contribution to Bone Metastasis Morbidity
Abstract
The cytokine interleukin-6 (IL-6) is strongly implicated in primary prostate cancer (PrCa) growth and the progression to bone metastasis. While expression and localization of IL-6 and its receptors gp 130 and IL-6R have been studied in organ-confined PrCa, these key mediators of the IL-6/gp130 signaling pathway have not been previously assessed in prostatic bone metastases. Thus far, our investigations with archival patient biopsies revealed that all PrCa bone metastases examined (n=14) expressed IL-6 on an overwhelming majority of cells (78 +/- 5%). The IL-6 receptor (IL-6R) was expressed in 11/14 cases in 77 +/- 7% of PrCa cells. Activated (phosphorylated) gp130 was expressed in all but one case (13/14), and was expressed in the majority of cells (79 +/- 5%) in 9/14 cases. Importantly, when IL-6R was localized to cell membranes (4/11 cases), phospho-gp130 and IL-6 were also detected at the cell membrane. Thus, members of the IL-6/GP130 axis are present in a high proportion of bone metastatic PrCa cells in most cases. The importance of this pathway will be further elucidated by characterizing anti-IL-6- treated BM18 transplants. Understanding the role of IL-6/gp130 signaling in this disease may lead to identification of novel targets and therapeutic strategies to improve and extend the quality of life for PrCa patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA469521
Entities
People
- Richard P. Redvers
Organizations
- University of Melbourne