Distribution, Levels, and Relevance of the Interleukin-1 Family of Cytokines and Receptors in Human Breast Carcinoma-Induced Osteolysis

摘要

Bone metastasis in human breast carcinoma (HBC) occurs in 83% of patients with advanced disease HBC bone metastasis causes degeneration of the bone matrix (osteolysis) hypercalcemia pathologic fracture and nerve- compression syndrome The pathophysiology of human breast carcinoma-induced osteolysis (HBC-IO) involves an increase in the number and activity of osteoclasts within the HBC metastatic lesion We examined the expression of the IL-I family of cytokines and receptors and IL-8 in HBC-IO using archival human samples (mean age 52 yrs; age range 34-83 yrs; no prior radiation to site) and immunohistochemistry We observed IL-I and IL-8 expression by HBC cells and IL-I Receptor I expression on osteoclasts. These data suggest that HBC-derived IL-I is an important mediator of human breast cancer-induced osteolysis and supports our hypothesis: 1) = IL-1 can activate osteoclastogenesis promote osteoclast (OC) activation and osteolysis via paracrine induction of IL-1 Receptors on osteoclasts. 2) IL-1 can promote tumor progression by autocrine induction and subsequent activation of IL-8. 3) IL-8 expressed by HBC cells can support tumor growth and progression by stimulating angiogenesis through IL-8 Receptors expressed on vascular endothelial cells. This study suggests that IL-1 may be an important mediator of HBC pathophysiology and therefore a potential target for therapeutic intervention.