Invasion and metastasis of cancer cells is a complex process requiring the activity of proteins that promote extracellular matrix degradation, motility of cancer cells, and angiogenesis. Although exclusively the cancer cells make several of these proteins, few key proteins are derived from stromal cells in response to cancer cell-stromal cell interaction. In this report, we show that the breast cancer cell-derived interleukinlalpha (IL-1 alpha) plays an important role in expression of pro-metastatic genes in cancer as well as in stromal cells. Neutralizing antibody against IL-1 alpha inhibited IL-6, and IL-8 expression in IL-1 alpha-expressing cancer cells. In addition, this antibody also prevented induction of IL-6, IL-8, and matrix metalloproteinase 3 (MMP3) but not vascular endothelial growth factor (VEGF) in fibroblasts by conditioned medium (CM) from IL-1 alpha-expressing breast cancer cells. These results suggest that inhibition of IL-1 alpha activity by either neutralizing antibody against IL-l alpha or chemical inhibitor of IL-1 alpha processing may prevent invasion and metastasis of breast cancer.