Role of Interleukin-6/GP130 Signaling in Prostate Cancer Progression and its Contribution to Bone Metastasis Morbidity

摘要

Prostate cancer (PrCa) is the leading cause of male cancer death in Western civilization. Interleukin-6 (IL-6) is a cytokine implicated in primary PrCa growth and survival post-androgen withdrawal. Moreover, IL-6 is strongly associated with bone metastasis, a major cause of morbidity in PrCa patients. This project aims to investigate the IL-6 axis in a novel in vivo PrCa xenograft model (BM18) of androgen-dependent growth (McCulloch et al., 2005) and osteosclerotic bone metastasis. The IL- 6/gp130 signaling pathway was also investigated using PrCa bone metastases from human patient biopsies. Pursuit of the aims outlined herein will greatly improve our understanding of the role of IL- 6/gp130 signaling in prostate cancer growth, regression, survival post- androgen withdrawal and bone metastasis. This study provides a unique opportunity to examine the role of IL-6/gp130 signaling in a model that closely mimics human PrCa growth, progression and regression as well as osteosclerotic bone remodeling. Disease recurrence and osteosclerotic metastases are poorly understood processes that cause immense suffering, culminating in a painful demise. Understanding the role of IL-6/gp130 signaling molecules in this disease may lead to identification of novel targets and therapeutic strategies to improve and extend the quality of life for PrCa patients.