The Novel Serine Protease Tumor-Associated Differentially Expressed Gene-15 (Matriptase/MT-SP1) Is Highly Overexpressed in Cervical Carcinoma

Alessandro D. Santin, Stefania Cane, Stefania Bellone, Eliana Bignotti, Michela Palmieri, Luis E. De Las Casas, Simone Anfossi, Juan J. Roman, Timothy O'Brien, Sergio Pecorelli

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND. Tumor-associated differentially expressed gene-15 (TADG-15/matriptase/MT-SP1) is a novel transmembrane serine protease involved in numerous biologic processes, including activation of growth and angiogenic factors and degradation of extracellular matrix components. To assess the value of TADG-15 as a possible marker for tumor detection and/or as a target for therapeutic intervention, the authors investigated the frequency of expression of TADG-15 in human cervical tumors. METHODS. TADG-15 expression was evaluated in 19 cervical carcinoma cell lines (i.e., 11 primary tumor cell lines and 8 established cell lines) and in 8 normal cervical keratinocyte control cultures using reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, to validate gene expression data at the protein level, TADG-15 expression was evaluated by immunohistochemistry on paraffin embedded tissue from which all 11 primary tumor cell lines were established. RESULTS. TADG-15 was expressed at high levels in 8 of 11 (73%) primary cervical carcinoma cell lines and in 6 of 8 (75%) established cervical carcinoma cell lines by RT-PCR. Expression of TADG-15 was found in 6 of 6 (100%) primary squamous cell cervical carcinomas, whereas 2 of 5 (40%) primary adenocarcinomas expressed TADG-15. In contrast, none of the normal cervical keratinocyte control cultures (n = 4) or flash-frozen normal cervical biopsy specimens (n = 4) expressed TADG-15. Immunohistochemistry staining of paraffin embedded cervical carcinoma specimens confirmed TADG-15 expression in tumor cells and its absence on normal cervical epithelial cells. CONCLUSIONS. Cervical carcinoma cells expressed high levels of TADG-15, suggesting that this protease may play an important role in invasion and metastasis. Because TADG-15 appears only in abundance in squamous tumor tissue and contains a proteolytic cleavage site, suggesting that the TADG-15 protease domain is released, it may prove to be a useful diagnostic tool for the early detection of recurrent/persistent cervical carcinoma after standard treatment or as a novel molecular target for therapy in patients with cervical carcinoma.

Original languageEnglish (US)
Pages (from-to)1898-1904
Number of pages7
JournalCancer
Volume98
Issue number9
DOIs
StatePublished - Nov 1 2003
Externally publishedYes

Keywords

  • Cervical carcinoma
  • Matriptase
  • Serine protease
  • Tumor-associated differentially expressed gene-15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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