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

Purpose: METH-1/hADAMTS-1 and METH-2/hADAMTS-8 are recently identified gene s that inhibit angiogenesis, and the murine homologue, ADAMTS-1, shows meta lloproteinase function. Because the significance of METH-1 and METH-2 has n ot been determined in solid tumors, we examined the mRNA expressions of the se 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 tran scription-PCR in 18 paired samples of pancreatic cancer and surrounding non cancerous pancreas, and in 14 samples of pancreatic cancer. METH-1 mRNA exp ression was also examined in 16 pairs of HCC and cirrhotic liver. Vasculari ty was estimated by CD34 staining. The correlation between clinicopathologi cal 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 ca ncer and noncancerous pancreas, but METH-2 was not. METH-1 expression in pa ncreatic cancer tissue was significantly lower than that in non-cancerous p ancreas (P = 0.002), and a similar result was obtained between HCC and cirr hotic liver (P = 0.003). METH-1 expression did not show a significant corre lation 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, respe ctively) and worse prognosis (P = 0.038). Conclusions: METH-1, which was initially reported to have a potent antiangi ogenic. effect, does not seem to be a predominant determinant of tumor vasc ularity in pancreatic cancer. Rather, METH-1 seems to be involved in progre ssion of pancreatic cancer through local invasion and lymph node metastasis .