RHAMM (CD168) is overexpressed on the protein level and may constitute an immunogenic antigen in advanced prostate cancer disease

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5129 Introduction: Treatment options for early stage prostate cancer are well defined, and localized prostate cancer can be cured by several strategies. However therapeutic outcome in advanced tumor stages is still disappointing. One approach is to deliver targeted therapy based on identified human tumor antigens, specifically expressed in neoplastic tissue and recognised by CD4/CD8 T-cells or antibodies. Materials and Methods: We employed serological identification of antigens by recombinant expression cloning (SEREX) and data mining in SEREX related databases to identify potential immunological target structures. Consequently, candidate antigens were screened by DNA microarrays consisting of approximately 20K genes, designed to profile benign and malignant prostate tissues. Genes overexpressed on the cDNA level were evaluated on the protein level by tissue microarrays representing various disease stages including about 900 tissue cores. Protein expression was measured by the Chromavision system. Results: Ten of the targets identified by SEREX and data mining showed a significant overexpression on the 20k cDNA array in localized prostate cancer compared to benign prostatic hyperplasia and in metastases compared to localized prostate cancer. One gene which has been identified earlier as an immunogenic antigen in leukemia by our group, CD168, showed a highly significant overexpression in prostate cancer metastases compared to localized disease (p=0.007). On the protein level CD168 was highest in metastatic tissue samples and significantly higher in neoplastic localized disease compared to benign tissue (p=0.03). High CD168 expression had an association to clinical parameters known to be associated with better clinical outcome. Patients with high CD168 expression in the primaries had a significantly lower risk for biochemical failure (log rank p=0.023; RR:0.621). In cell culture experiments, the number of viable cells was reduced in blocking experiments using hormone sensitive (LNCaP) and hormone insensitive metastatic (PC3 and DU 145) prostate cancer cell lines. Conclusion: Acknowledging the proven immunogenic effects of CD168 in leukemia, this antigen is an intriguing therapeutic target in advanced prostate cancer disease. No significant financial relationships to disclose.