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Expression of METH-1 and METH-2 in pancreatic cancer
1Department of Surgery and Surgical Basic Science, School of Medicine, Kyoto University, 54-Shogoin Kawara-cho, Sakyo, Kyoto 606-8507, Japan. masui@kuhp.kyoto-u.ac.jp
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.
Insights
METH-1 (metalloproteinase with thrombospondin type 1 motif, member 1) expression is reduced in pancreatic cancer and hepatocellular carcinoma. It appears to promote cancer progression via invasion and metastasis, not by affecting tumor vascularity.
Area of Science:
- Oncology
- Molecular Biology
- Gene Expression Analysis
Background:
- METH-1 (metalloproteinase with thrombospondin type 1 motif, member 1) and METH-2 (metalloproteinase with thrombospondin type 1 motif, member 8) are newly identified genes with anti-angiogenic properties.
- The role of METH-1 and METH-2 in solid tumors, specifically pancreatic cancer and hepatocellular carcinoma (HCC), remains largely undetermined.
- The murine homologue, ADAMTS-1, exhibits metalloproteinase activity, suggesting potential functional roles for METH-1 and METH-2.
Purpose of the Study:
- To investigate the mRNA expression levels of METH-1 and METH-2 in pancreatic cancer and HCC.
- To determine the correlation between METH-1 expression and clinicopathological factors, including tumor vascularity, metastasis, and prognosis.
- To elucidate the functional significance of METH-1 in the progression of pancreatic cancer.
Main Methods:
- Quantification of METH-1 and METH-2 mRNA expression using TaqMan reverse transcription-PCR in pancreatic cancer cell lines and paired tumor/non-tumor tissues.
- Examination of METH-1 mRNA expression in HCC and cirrhotic liver samples.
- Assessment of tumor vascularity via CD34 staining and statistical analysis of METH-1 expression in relation to clinicopathological variables.
Main Results:
- METH-1 was expressed in pancreatic cancer cell lines, but METH-2 expression was limited.
- METH-1 mRNA levels were significantly lower in pancreatic cancer and HCC tissues compared to their non-cancerous counterparts.
- While METH-1 did not correlate with tumor vascularity, higher METH-1 expression was associated with increased lymph node metastasis, retroperitoneal invasion, and poorer prognosis in pancreatic cancer.
Conclusions:
- METH-1's anti-angiogenic potential does not appear to be a primary driver of tumor vascularity in pancreatic cancer.
- METH-1 is implicated in the progression of pancreatic cancer, potentially through mechanisms involving local invasion and lymph node metastasis.
- Further research is warranted to fully understand METH-1's role in cancer pathogenesis and its therapeutic implications.