Nozaki S, Sledge G W, Nakshatri H
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA.
Biochem Biophys Res Commun. 2000 Aug 18;275(1):60-2. doi: 10.1006/bbrc.2000.3241.
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.
癌细胞的侵袭和转移是一个复杂的过程，需要多种蛋白质发挥作用，这些蛋白质可促进细胞外基质降解、癌细胞迁移及血管生成。虽然这些蛋白质中有几种仅由癌细胞产生，但少数关键蛋白质是基质细胞在与癌细胞相互作用时产生的。在本报告中，我们表明乳腺癌细胞衍生的白细胞介素-1α（IL-1α）在癌细胞和基质细胞中促转移基因的表达中发挥重要作用。抗IL-1α中和抗体抑制了表达IL-1α的癌细胞中IL-6和IL-8的表达。此外，该抗体还可防止表达IL-1α的乳腺癌细胞的条件培养基（CM）诱导成纤维细胞中IL-6、IL-8和基质金属蛋白酶3（MMP3）的产生，但不能防止血管内皮生长因子（VEGF）的产生。这些结果表明，通过抗IL-1α中和抗体或IL-1α加工的化学抑制剂抑制IL-1α活性，可能会阻止乳腺癌的侵袭和转移。
