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The novel serine protease tumor‐associated differentially expressed gene–15 ( matriptase / MT‐SP1 ) is highly overexpressed in cervical carcinoma
Author(s) -
Santin Alessandro D.,
Cane' Stefania,
Bellone Stefania,
Bignotti Eliana,
Palmieri Michela,
De Las Casas Luis E.,
Anfossi Simone,
Roman Juan J.,
O'Brien Timothy,
Pecorelli Sergio
Publication year - 2003
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.11753
Subject(s) - cell culture , immunohistochemistry , pathology , epidermoid carcinoma , carcinoma , medicine , cancer research , extracellular matrix , biology , microbiology and biotechnology , genetics
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. Cancer 2003. © 2003 American Cancer Society.