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

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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 - 28-11-2001

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Masui, T., Hosotani, R., Tsuji, S., Miyamoto, Y., Yasuda, S., Ida, J., Nakajima, S., Kawaguchi, M., Kobayashi, H., Koizumi, M., Toyoda, E., Tulachan, S., Arii, S., Doi, R., & Imamura, M. (2001). Expression of METH-1 and METH-2 in pancreatic cancer. Clinical Cancer Research, 7(11), 3437-3443.