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Expression of METH-1 and METH-2 in Pancreatic Cancer
Ist Teil von
Clinical cancer research, 2001-11, Vol.7 (11), p.3437-3443
Ort / Verlag
United States: American Association for Cancer Research
Erscheinungsjahr
2001
Quelle
MEDLINE
Beschreibungen/Notizen
Purpose: 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).
Experimental Design: 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.