Cancer cell-derived interleukin 1α contributes to autocrine and paracrine induction of pro-metastatic genes in breast cancer

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 interleukin-1alpha (IL-1α) plays an important role in expression of pro-metastatic genes in cancer as well as in stromal cells. Neutralizing antibody against IL-1α inhibited IL-6, and IL-8 expression in IL-1α-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-1α-expressing breast cancer cells. These resuits suggest that inhibition of IL-1α activity by either neutralizing antibody against IL-1α or chemical inhibitor of IL-1α processing may prevent invasion and metastasis of breast cancer. (C) 2000 Academic Press.