Abstract
Background: METI-I-1 and METI-I-2 are newly identified gene that show sequence similarity to metalloproteinase, disintegrin and TSP type1 repeats. METH-1 and -2 have antiangiogenic properties and murine homotogue of METH-1 shows metalloproteinese function. However, the significance of METH-1 and -2 has not yet been determined in human solid tumors. In this study, we examined METH-1 and -2 mRNA expressions in two tumors with distinct differences in vasculadty, pancreatic ductal adenocarcinoma and hepatocelluier carcinoma (HCC). Methods: METH-1 and -2 mRNA expressions were identified in 6 pancreatic cancer cell lines, and then examined in surgically resected samples of 32 pancreatic cancer, 20 pancreas, 16 HCC and 16 liver cirrhosis. METH-1 and -2 gene expressions were measured by RT-PCR and quantltated by TaqMan RT-PCR assay using beta-actin as an internal standard and expressed as a METH-1/beta-actin or METH-2/beta-actin mRNA ratio. Vascularity of tumor was estimated by CD34 staining. Correlation of METH-1 mRNA expression with clinicopathological factors were further analyzed in 32 patients with pancreatic cancer. Results: 4 out of 6 pancreatic cancer cell lines expressed METH-1 and none expressed METH-2. METH-1 mRNA was substantially expressed in both pancreatic cancer and pancreas tissue, hot METH-2 did not. When quantitated with TaqMan RT-PCR, METH-1 mHNA expression in pancreatic cancer tissue was significantly lower than that in non-cancerous lesion of pancreas (p = 0.002), and similar results were obtained between HCC and cirrhotic liver (p = 0.003). Reduction of METH1 mRNA expression in pancreatic cancer was nearly equal with that in HCC. The expression of METH-1 had no significant correlation with MVD (Mean Vascular Density) in pancreatic cancer tissue and HOG. However, pancreatic cancer with high expression of METH-1 significantly increased lymph node metastasis or severe retroperitoneal invasion (p=0.033 and p = 0.039, respectively). There were no significant correlations between METH-1 expression and tumor size or histological grade. Patients with high METH-1 expression showed significantly worse prognosis than those with low METH-1 (p=0.032). Conclusions: METH-f, which is initially reported to have a very potent antiangiogenetic property, does not seem to be a predominant factor to determine the tumor vascularity in pancreatic cancer and HCC, but lowered expression of METH-1 might be involved in tumor angiogenesis. METH-1 is rather involved in progression of pancreatic cancer through local invasion and lymphnode metastasis.
Published Version
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