Neutrophil activator of matrix metalloproteinase-2 (NAM)

被引：0
作者：
Ellen E. Rollo
Michelle Hymowitz
Cathleen E. Schmidt
Steve Montana
Hussein Foda
Stanley Zucker
机构：
[1] Veterans Affairs Medical Center,Departments of Research and Medicine
[2] State University of New York at Stony Brook,School of Medicine
来源：
Clinical & Experimental Metastasis | 2006年 / 23卷
关键词：
Extracellular matrix; Matrix metalloproteinase (MMP); Metastasis; MMP activation; Neutrophil; Cancer;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
We have isolated a novel soluble factor(s), neutrophil activator of matrix metalloproteinases (NAM), secreted by unstimulated normal human peripheral blood neutrophils that causes the activation of cell secreted promatrix metalloproteinase-2 (proMMP-2). Partially purified preparations of NAM have been isolated from the conditioned media of neutrophils employing gelatin-Sepharose chromatography and differential membrane filter centrifugation. NAM activity, as assessed by exposing primary human umbilical vein endothelial cells (HUVEC) or HT1080 cells to NAM followed by gelatin zymography, was seen within one hour. Tissue inhibitor of metalloproteinase-2 (TIMP-2) and hydroxamic acid derived inhibitors of MMPs (CT1746 and BB94) abrogated the activation of proMMP-2 by NAM, while inhibitors of serine and cysteine proteases showed no effect. NAM also produced an increase in TIMP-2 binding to HUVEC and HT1080 cell surfaces that was inhibited by TIMP-2, CT1746, and BB94. Time-dependent increases in MT1-MMP protein and mRNA were seen following the addition of NAM to cells. These data support a role for NAM in cancer dissemination.
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页码：259 / 268
页数：9
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  • [1] Hanahan D(2000)The hallmarks of cancer Cell 100 57-70
  • [2] Weinberg RA(2001)Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment Oncogene 19 6642-6650
  • [3] Zucker S(2005)Smoldering and polarized inflammation in the initiation and promotion of malignant disease Cancer Cell 7 211-217
  • [4] Cao J(2002)Inflammation and cancer Nature 420 860-867
  • [5] Chen W-T(2001)Colony stimulating factor 1 promotes progression of mammary tumors to malignancy J Exp Med 193 727-740
  • [6] Balkwill F(2004)NF-kB functions as a tumour promotor in inflammation-associated cancer Nature 431 461-466
  • [7] Charles KA(1999)The cell biology of leukocyte-mediated proteolysis J Leukoc Biol 65 137-150
  • [8] Mantovani A(2006)Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells Blood 107 317-327
  • [9] Coussens LM(2003)Role of pericellular proteolysis by membrane-type 1 matrix metalloproteinase in cancer invasion and angiogenesis Cancer Metastasis Rev 22 129-143
  • [10] Werb Z(1995)Prognostic significance of three novel biologic factors in a clinical trial of adjuvant therapy for node-negative breast cancer Surgery 117 601-608
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