RHAMM (CD168) is overexpressed at the protein level and may constitute an immunogenic antigen in advanced prostate cancer disease.
Localized prostate cancer (CaP) can be cured using several strategies. However, the need to identify active substances in advanced tumor stages is tremendous, as the outcome in such cases is still disappointing. One approach is to deliver human tumor antigen-targeted therapy, which is recognized by T cells or antibodies. We used data mining of the Cancer Immunome Database (CID), which comprises potential immunologic targets identified by serological screening of expression libraries. Candidate antigens were screened by DNA microarrays. Genes were then validated at the protein level by tissue microarrays, representing various stages of CaP disease. Of 43 targets identified by CID, 10 showed an overexpression on the complementary DNA array in CaP metastases. The RHAMM (CD168) gene, earlier identified by our group as an immunogenic antigen in acute and chronic leukemia, also showed highly significant overexpression in CaP metastases compared with localized disease and benign prostatic hyperplasia. At the protein level, RHAMM was highest in metastatic tissue samples and significantly higher in neoplastic localized disease compared with benign tissue. High RHAMM expression was associated with clinical parameters known to be linked to better clinical outcome. Patients with high RHAMM expression in the primaries had a significantly lower risk of biochemical failure. The number of viable cells in cell cultures was reduced in blocking experiments using hormone-sensitive and hormone-insensitive metastatic CaP cell lines. Acknowledging the proven immunogenic effects of RHAMM in leukemia, this antigen is intriguing as a therapeutic target in far-advanced CaP.
Gust
Kilian M
KM
Department of Urology, University of Ulm, Ulm, Germany.
Hofer
Matthias D
MD
Perner
Sven R
SR
Kim
Robert
R
Chinnaiyan
Arul M
AM
Varambally
Sooryanarayana
S
Moller
Peter
P
Rinnab
Ludwig
L
Rubin
Mark A
MA
Greiner
Jochen
J
Schmitt
Michael
M
Kuefer
Rainer
R
Ringhoffer
Mark
M
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D049109:Cell Proliferation; D016208:Databases, Factual; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor