The Role of Osteoblast-Derived Cytokines in Bone Metastatic Breast Cancer
Abstract
Breast cancer (BC) metastasizes to bone. It is likely bone provides a hospitable environment that attracts BC cells and allows them to colonize and grow. Current models suggest BC-derived cytokines are key to understanding BC metastasis. We hypothesize that osteoblasts can be directed by metastatic BC cells to produce cytokines that are chemoattractants for osteoclasts and cancer cells, and growth or maintenance factors for BC cells. Our purpose is to determine how osteoblast-derived cytokines influence BC metastases to bone. Goals include investigating the production of osteoblast-derived cytokines in response to BC cells or their conditioned medium (CM), the production of bone-derived cytokines in response to BC cells in vivo, and the presence of functional cytokine receptors on osteoblasts and BC cells. Using murine osteoblasts, and human metastatic BC and non-metastatic cells, we found that BC CM treatment increased osteoblast-derived cytokine secretion of IL-6, KC, VEGF, MIP-2, and MCP-1. Maximum induction of osteoblast-derived cytokine secretion occurred with 20 day old cells. Treatment with CM of a bone-seeking cancer variant enhanced osteoblast-derived cytokine production at Day 20. Murine-specific ELISAs showed osteoblast-derived cytokine secretion to MDA-231 variant CM was dose-dependent. No significant changes in osteoblast-derived cytokine secretion were observed in 4 day old cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA471009
Entities
People
- Karen M Bussard
Organizations
- Pennsylvania State University