Tumor-related protein, the squamous cell carcinoma antigen binds to the intracellular protein carbonyl reductase

Squamous cell carcinoma antigen (SCCA) is a useful tumor marker for diagnosis and management of squamous cell carcinoma. Recent reports have shown that SCCA can influence the invasion or metastasis of cancer cells. However, it remained unclear how SCCA acts to mediate these biological functions. To solve this question, at first, SCCA1- and SCCA2-glutathione S-transferase fusion protein were used to purify a protein which binds to SCCA1 or SCCA2, and the combined protein was identified by proteomic analysis. Secondly, immunocytochemical and immunohistochemical analyses were performed to investigate the localization of this protein. Third, Western blotting was performed to analyze the expression levels of this protein in keratinocytes and six kinds of uterine squamous cell carcinoma cell lines. Both SCCA1 and SCCA2 molecules bind to the cytoplasmic protein, which was identified to be carbonyl reductase (CR). The immunostaining analyses revealed that CR is located in the cytoplasm of keratinocytes and the normal squamous epithelial cells of the uterine cervix as well as SCCA1 and SCCA2. The CR expression levels in six kinds of squamous cell carcinoma cell lines were lower compared to those in keratinocytes. In conclusion, CR binds to SCCA1 and SCCA2 and they are co-located in the same layer of the squamous epithelium, suggesting that CR may collaborate with SCCA1 and SCCA2 to mediate cancer behavior such as invasion or metastasis.