The Multifaceted Role of Osteopontin in Prostate Pathologies

Abstract

The prostate gland, located beneath the bladder and surrounding the proximal urethra in men, plays a vital role in reproductive physiology and sexual health. Despite its importance, the prostate is vulnerable to various pathologies, including prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Osteopontin (OPN), a versatile protein involved in wound healing, inflammatory responses, and fibrotic diseases, has been implicated in all three prostate conditions. The role of OPN in prostatic pathophysiology, affecting both benign and malignant prostate conditions, is significant. Current evidence strongly suggests that OPN is expressed at a higher level in prostate cancer and promotes tumor progression and aggressiveness. Conversely, OPN is primarily secreted by macrophages and foam cells in benign prostate conditions and provokes inflammation and fibrosis. This review discusses the accumulating evidence on the role of OPN in prostatic diseases, cellular sources, and potential roles while also highlighting areas for future investigations.

Keywords: benign prostatic hyperplasia; foam cells; prostate cancer; prostatitis.

Figure 1

OPN-mediated cell signaling events suggested in benign prostate pathologies. Abbreviations/protein names: CXCL1/2/8: chemokine (C-X-C motif) ligand 1/2/8, MMP1: matrix metalloproteinase 1, OPN: osteopontin.

Figure 2

OPN-mediated cell signaling events identified in prostate cancer cells. Abbreviations/protein names: COX-2: Cyclooxygenase-2, c-SRC: Proto-oncogene tyrosine-protein kinase Src, EGFR: Epidermal growth factor receptor, ERK: Extracellular signal-regulated kinase, FAK: Focal adhesion kinase, IκBα: NF kappa B inhibitor α, IKKα/β: IkappaB kinase α/β, MEK: Mitogen-activated protein kinase, NIK: NF-κB-inducing kinase, OPN: Osteopontin, p50: Nuclear factor κ-light-chain-enhancer of activated B cells/NFκB, p65: NFκB p65 subunit, P-gp: P-glycoprotein, PI3K: Phosphoinositide 3-kinase.