Cancer cell-derived interleukin 1alpha 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-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.
Nozaki
S
S
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA.
Sledge
G W
GW
Nakshatri
H
H
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D019898:Autocrine Communication / Q000187:drug effects*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D019899:Paracrine Communication / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019278:Matrix Metalloproteinase 3