Expression of METH-1 and METH-2 in pancreatic cancer.
OBJECTIVE
METH-1/hADAMTS-1 and METH-2/hADAMTS-8 are recently identified genes that inhibit angiogenesis, and the murine homologue, ADAMTS-1, shows metalloproteinase function. Because the significance of METH-1 and METH-2 has not been determined in solid tumors, we examined the mRNA expressions of these molecules in pancreatic cancer and hepatocellular carcinoma (HCC).


METHODS
METH-1 and METH-2 mRNA expressions were identified in six pancreatic cancer cell lines and were quantified by TaqMan reverse transcription-PCR in 18 paired samples of pancreatic cancer and surrounding noncancerous pancreas, and in 14 samples of pancreatic cancer. METH-1 mRNA expression was also examined in 16 pairs of HCC and cirrhotic liver. Vascularity was estimated by CD34 staining. The correlation between clinicopathological factors and METH-1 expression was additionally analyzed.


RESULTS
Four of six pancreatic cancer cell lines expressed METH-1, and 1/6 expressed METH-2. METH-1 was substantially expressed in both pancreatic cancer and noncancerous pancreas, but METH-2 was not. METH-1 expression in pancreatic cancer tissue was significantly lower than that in noncancerous pancreas (P = 0.002), and a similar result was obtained between HCC and cirrhotic liver (P = 0.003). METH-1 expression did not show a significant correlation with vascularity in pancreatic cancer or in HCC. However, pancreatic cancer with higher expression of METH-1 showed significantly severe lymph node metastasis or retroperitoneal invasion (P = 0.033 and P = 0.018, respectively) and worse prognosis (P = 0.038).


CONCLUSIONS
METH-1, which was initially reported to have a potent antiangiogenic effect, does not seem to be a predominant determinant of tumor vascularity in pancreatic cancer. Rather, METH-1 seems to be involved in progression of pancreatic cancer through local invasion and lymph node metastasis.
Masui
T
T
Department of Surgery and Surgical Basic Science, School of Medicine, Kyoto University, 54-Shogoin Kawara-cho, Sakyo, Kyoto 606-8507, Japan. masui@kuhp.kyoto-u.ac.jp
Hosotani
R
R
Tsuji
S
S
Miyamoto
Y
Y
Yasuda
S
S
Ida
J
J
Nakajima
S
S
Kawaguchi
M
M
Kobayashi
H
H
Koizumi
M
M
Toyoda
E
E
Tulachan
S
S
Arii
S
S
Doi
R
R
Imamura
M
M
D051722:ADAM Proteins; D000071096:ADAMTS Proteins; D000071097:ADAMTS1 Protein; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D019483:Disintegrins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D008666:Metalloendopeptidases / Q000235:genetics*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D019483:Disintegrins; D012313:RNA; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; C120807:ADAMTS8 protein, human; D008666:Metalloendopeptidases