title: Human macrophage metalloelastase worsens the prognosis of pancreatic cancer.
abstract: OBJECTIVE
  To evaluate the role of human macrophage metalloelastase (HME) in pancreatic cancer.
  
  
  BACKGROUND
  HME, a member of the human matrix metalloproteinase family, possesses elastolytic activity and is critical for the degradation of extracellular matrix proteins. Inasmuch as tumor invasion and metastasis formation require lysis of extracellular matrix, HME plays a critical role in both processes.
  
  
  METHODS
  HME expression was analyzed by Northern blot analysis, reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry in 39 pancreatic cancer tissues and 13 normal controls. The molecular data were related to clinicopathologic parameters and patient survival.
  
  
  RESULTS
  In human pancreatic cancer, overexpression of HME mRNA was present in 25 of 39 pancreatic cancer tissues (64%) and in five pancreatic cancer cell lines. In contrast, low levels of HME mRNA expression were present in 13 normal pancreatic tissues samples. By Western blot analysis, high levels of HME were found in pancreatic cancer tissues and in the pancreatic cancer cell lines compared with the normal controls. Fifty-six percent of the cancer samples exhibited HME immunoreactivity in the cancer cells, and 63% in the stromal cells. Analysis of the survival data revealed that patients whose tumors exhibited HME mRNA overexpression lived significantly shorter compared with patients whose tumors did not overexpress HME. No relationship between HME expression and tumor stage, tumor grading, or presence of lymph node metastases was found.
  
  
  CONCLUSIONS
  These findings indicate that HME participates in pancreatic cancer progression and that its presence worsens the prognosis. These data suggest a benefit of its inhibition in the treatment of pancreatic cancer.
authors.affiliation: Department of General Surgery, University of Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Balaz
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kondo
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Zhu
authors.forename: Arthur
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
mesh_terms: D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000473:pathology
chemical_list: D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12