The Distribution, Levels, and Relevance of the Interleukin-1 Family of Cytokines and Receptors in Human Breast Carcinoma-Induced Osteolysis
Abstract
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-1 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-1 and IL-8 expression by HBC cells and IL-1 Receptor I expression on osteoclasts. These data suggested that HBC-derived IL-1 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA433931
Entities
People
- Alexander G. Pantschenko
Organizations
- University of Connecticut Health Center