Prognostic significance of tissue factor pathway inhibitor-2 in pancreatic carcinoma and its effect on tumor invasion and metastasis.

Abstract

Tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated kunitz-type serine proteinase inhibitor that plays an important role in plasmin and trypsin-mediated activation of zymogen matrix metalloproteinases involved in tumor angiogenesis, invasion and metastasis. Earlier studies have shown that the production of TFPI-2 is downregulated during the progression of various tumors. To detect whether TFPI-2 can be expressed in human pancreatic carcinoma samples, to evaluate its prognostic significance on pancreatic carcinoma and to investigate its effect on tumor invasion and metastasis, we collected 9 normal pancreatic tissue samples and 41 pancreatic carcinoma samples and stably transfected the human pancreatic carcinoma cell line Panc-1 with a vector capable of expressing TFPI-2 gene. RT-PCR and Western blot analysis revealed that the expression of TFPI-2 in pancreatic carcinoma samples was markedly lower than that in normal pancreas samples, and there was no TFPI-2 expression in Panc-1 cell. Its expression was related with biological characters of pancreatic carcinoma. The results of Boyden chamber assay and orthotopic pancreatic carcinoma model showed that TFPI-2 could inhibit invasion and metastasis ability of pancreatic carcinoma in vitro and in vivo. Kaplan-Meier survival curve and Cox proportional hazards model assay identified TFPI-2 as an independent prognostic factor for pancreatic carcinoma. Our data suggest that TFPI-2 plays a significant role in the invasion and metastasis of pancreatic carcinoma cell in vitro and in vivo and is determined to be an important prognostic factor for pancreatic carcinoma patients.

• Authors: Zhigang Tang, Guangyong Geng, Qiang Huang, Geliang Xu, Hejie Hu, Jiong Chen, Jiansheng Li
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 27 Issue 3 Pg. 867-75 (Sep 2010) ISSN: 1559-131X [Electronic] United States
• PMID: 19763915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycoproteins
• Neoplasm Proteins
• RNA, Messenger
• RNA, Neoplasm
• Recombinant Fusion Proteins
• tissue-factor-pathway inhibitor 2

Topics

• Adult
• Aged
• Animals
• Carcinoma (metabolism, mortality, pathology)
• Cell Line, Tumor (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Glycoproteins (analysis, genetics, physiology)
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Proteins (analysis, physiology)
• Neoplasm Transplantation
• Pancreatic Neoplasms (metabolism, mortality, pathology)
• Prognosis
• RNA, Messenger (biosynthesis)
• RNA, Neoplasm (biosynthesis)
• Recombinant Fusion Proteins (physiology)
• Young Adult