A novel role for tissue factor pathway inhibitor-2 in the therapy of human esophageal carcinoma

Yuliang Ran, Jian Pan, Hai Hu, Zhuan Zhou, Lichao Sun, Liang Peng, Long Yu, Lixin Sun, Jun Liu, Zhihua Yang*

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Esophageal cancer is characterized by rapid clinical progression and poor prognosis, due to early-stage invasion of adjacent tissues and metastasis. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. Here we describe the potential involvement of TFPI-2 in the development of esophageal carcinoma. Western blotting revealed that TFPI-2 was downregulated in 75% of esophageal carcinomas and in most esophageal carcinoma cell lines. Immunohistochemistry revealed that TFPI-2 was significantly downregulated in tumor tissues and in lymph node metastases. Experimental overexpression of TFPI-2 in KYSE450, KYSE510, YES2, and EC9706 cells significantly inhibited their invasive ability. Overexpression of TFPI-2 in EC9706 cells inhibited xenograft tumor growth and invasion into surrounding tissues, as well as reduced lung metastasis. Further studies demonstrated that recombinant TFPI-2 protein significantly inhibited the activity of matrix metalloproteinases and tumor-related angiogenesis. Parenteral treatment with recombinant TFPI-2 protein significantly suppressed xenograft growth and metastasis. Together, these data indicate that TFPI-2 inhibits tumor invasion and angiogenesis both in vitro and in vivo, and suggest a potentially important therapeutic role for recombinant TFPI-2 in the treatment of malignant esophageal carcinomas.

Original languageEnglish (US)
Pages (from-to)41-49
Number of pages9
JournalHuman Gene Therapy
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Ran, Y., Pan, J., Hu, H., Zhou, Z., Sun, L., Peng, L., Yu, L., Sun, L., Liu, J., & Yang, Z. (2009). A novel role for tissue factor pathway inhibitor-2 in the therapy of human esophageal carcinoma. Human Gene Therapy, 20(1), 41-49. https://doi.org/10.1089/hum.2008.129