PMID- 10944441 OWN - NLM STAT- MEDLINE DCOM- 20000921 LR - 20061115 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 275 IP - 1 DP - 2000 Aug 18 TI - Cancer cell-derived interleukin 1alpha contributes to autocrine and paracrine induction of pro-metastatic genes in breast cancer. PG - 60-2 AB - 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-1alpha) plays an important role in expression of pro-metastatic genes in cancer as well as in stromal cells. Neutralizing antibody against IL-1alpha inhibited IL-6, and IL-8 expression in IL-1alpha-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-1alpha-expressing breast cancer cells. These results suggest that inhibition of IL-1alpha activity by either neutralizing antibody against IL-1alpha or chemical inhibitor of IL-1alpha processing may prevent invasion and metastasis of breast cancer. CI - Copyright 2000 Academic Press. FAU - Nozaki, S AU - Nozaki S AD - Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA. FAU - Sledge, G W Jr AU - Sledge GW Jr FAU - Nakshatri, H AU - Nakshatri H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Antibodies) RN - 0 (Culture Media, Conditioned) RN - 0 (Endothelial Growth Factors) RN - 0 (Growth Inhibitors) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (LIF protein, human) RN - 0 (Leukemia Inhibitory Factor) RN - 0 (Lymphokines) RN - 0 (Neoplasm Proteins) RN - 0 (RNA, Messenger) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Vascular Endothelial Growth Factors) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Antibodies/immunology/pharmacology MH - Autocrine Communication/*drug effects MH - Breast Neoplasms/*genetics/metabolism/*pathology MH - Culture Media, Conditioned/pharmacology MH - Endothelial Growth Factors/genetics MH - Fibroblasts/drug effects/metabolism MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Growth Inhibitors/antagonists & inhibitors/immunology/pharmacology MH - Humans MH - Interleukin-1/antagonists & inhibitors/immunology/*pharmacology MH - Interleukin-6/genetics MH - Interleukin-8/genetics MH - Leukemia Inhibitory Factor MH - Lymphokines/antagonists & inhibitors/genetics/immunology/pharmacology MH - Matrix Metalloproteinase 3/genetics MH - Neoplasm Invasiveness/genetics MH - Neoplasm Metastasis/genetics MH - Neoplasm Proteins/genetics MH - Paracrine Communication/*drug effects MH - RNA, Messenger/metabolism MH - Tumor Cells, Cultured MH - Vascular Endothelial Growth Factor A MH - Vascular Endothelial Growth Factors EDAT- 2000/08/17 11:00 MHDA- 2000/09/23 11:01 CRDT- 2000/08/17 11:00 PHST- 2000/08/17 11:00 [pubmed] PHST- 2000/09/23 11:01 [medline] PHST- 2000/08/17 11:00 [entrez] AID - S0006-291X(00)93241-8 [pii] AID - 10.1006/bbrc.2000.3241 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2000 Aug 18;275(1):60-2. doi: 10.1006/bbrc.2000.3241.