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A Novel Role for Tissue Factor Pathway Inhibitor-2 in the Therapy of Human Esophageal Carcinoma.
- Source :
-
Human Gene Therapy . Jan2009, Vol. 20 Issue 1, p41-49. 9p. - Publication Year :
- 2009
-
Abstract
- AbstractEsophageal 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 vitroand in vivo, and suggest a potentially important therapeutic role for recombinant TFPI-2 in the treatment of malignant esophageal carcinomas. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CANCER
*CRYOBIOLOGY
*TUMORS
*CELL lines
*CELL culture
Subjects
Details
- Language :
- English
- ISSN :
- 10430342
- Volume :
- 20
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Human Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 36232209
- Full Text :
- https://doi.org/10.1089/hum.2008.129