Expression of METH-1 and METH-2 in pancreatic cancer

  • T. Masui
  • , R. Hosotani
  • , S. Tsuji
  • , Y. Miyamoto
  • , S. Yasuda
  • , J. Ida
  • , S. Nakajima
  • , M. Kawaguchi
  • , H. Kobayashi
  • , M. Koizumi
  • , E. Toyoda
  • , S. Tulachan
  • , S. Arii
  • , R. Doi
  • , M. Imamura

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

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 non-cancerous 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.

Original languageEnglish
Pages (from-to)3437-3443
Number of pages7
JournalClinical Cancer Research
Volume7
Issue number11
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • General Medicine

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