Search for molecules which bind to SCC antigen, analysis of their functions and clinical significance, and application to the molecular target therapy

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The SCC antigen binds to the 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. Sense and antisense CR cDNAs were transfected into a human uterine SCC cell lines to investigate the role of CR in cancer cell invasion and metastasis. In an in vitro experiment, suppression of CR showed morphology changes to like fibroblast, increased cancer cell invasion, secretion of MMP. On the other hand, over-expression of CR decreased MMP secretion. Paraffin sections from uterine cervical SCC tissues, FIGO stage Ib1-IIb were immunostained with anti-CR antibodies. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method. Immunohistochemical analyses showed that reduced CR expression patterns in primary cancer lesions were closely associated with a high incidence of pelvic lymph node metastasis, poor OS, and poor PFS.