Human macrophage metalloelastase worsens the prognosis of pancreatic cancer.
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.
Balaz
Peter
P
Department of General Surgery, University of Heidelberg, Germany.
Friess
Helmut
H
Kondo
Yasuo
Y
Zhu
Zhaowen
Z
Zimmermann
Arthur
A
Büchler
Markus W
MW
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
D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12