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In our previous study, monoclonal antibody RM2, established toward the glycosyl epitope, reflected grade of malignancy of prostate cancer cells whereas RM2 reactivity to benign glands was negative or weak. RM2 reactivity was also detected in stroma, suggesting the glycoprotein RM2 recognizes could be released into the bloodstream. Then, we explored RM2 reactivity to sera of early prostate cancer. We compared RM2 reactivity to sera between 62 patients with early prostate cancer and 43 subjects with benign prostatic disease, and examined RM2 reactivity before and after radical prostatectomy in 15 patients by Western blotting. We also examined RM2 reactivity to sera of the other urogenital cancers. RM2 reactivity was significantly enhanced on a serum glycoprotein with molecular mass approximately 40 kDa, hereby termed GPX, in the patients with early prostate cancer when compared with those with benign prostatic disease (p < 0.0001). Setting an appropriate cutoff level, RM2 reactivity to GPX for detection of prostate cancer had sensitivity of 87% and specificity of 84%, respectively. Furthermore, the level of RM2 reactivity significantly decreased after radical prostatectomy (p = 0.006). However, increased RM2 reactivity to GPX was also observed in the other urogenital cancers. The proteomics approach identified GPX as haptoglobin-beta chain and RM2 showed preferential reactivity toward haptoglobin-beta chain derived from prostate cancer when compared with polyclonal anti-haptoglobin antibody. Haptoglobin-beta chain defined by RM2 is a novel serum marker that may be useful for detection of early prostate cancer when coupled with prostate-specific antigen because it is not specific to prostate cancer.

Although prostate-specific antigen (PSA) has been widely used for early detection of prostate cancer, PSA has problems with specificity and prediction of pathological stage. Therefore, a new marker for prostate cancer is urgently required. We examined expression of a novel carbohydrate antigen, beta1,4-GalNAc-disialyl-Lc(4), defined by the monoclonal antibody RM2, in prostate cancer using 75 cases of radical prostatectomy specimens. RM2 immunoreactivity was negative to weak in all benign glands, and weak to moderate in high-grade prostatic intraepithelial neoplasia. In prostatic adenocarcinoma, RM2 immunoreactivity was negative to weak (lower expression) in 20 cases, and moderate to strong (higher expression) in 55 cases. A clear difference of RM2 expression level was observed between Gleason patterns 3 and >/=4. Higher expression of RM2 antigen was significantly associated with primary Gleason pattern >/=4, high Gleason score (>/=8), larger tumor volume and advanced tumor stage. Furthermore, 5-year PSA failure-free survival was significantly lower in the higher expression group. However, no significant relationship was observed between RM2 expression level and preoperative serum PSA. Western blot analysis in prostate cancer cell lines PC3 and LNCap revealed that major 49-kDa and minor 39-kDa glycoproteins were common to both cells, but there was an increase of 59- and 125-kDa glycoproteins unique to LNCap and an increase of 88- and 98-kDa glycoproteins unique to PC3. RM2 antigen is a new histological marker for prostate cancer that may reflect the Gleason grading system. Identification of the glycoproteins carrying the RM2 antigen will provide new insights into the properties of prostate cancer., ((c) 2005 Wiley-Liss, Inc.)

Elevated expression of sialyl Lewis X has been postulated to be a prognostic indicator of prostate cancer. However, direct evidence for the relationship between increased expression of sialyl Lewis X and malignancy of prostate cancer is still lacking. To determine whether increased levels of sialyl Lewis X leads to malignancy in prostate tumor, we transfected the human prostate cancer cell line PC-3 with alpha1,3-fucosyltransferase III (FTIII) to obtain stable transfectants, PC-3-FTIII lines, that highly express sialyl Lewis X. When inoculated in the prostate of nude mice, PC-3-FTIII cells produced large prostate tumors, while mock-transfected PC-3 cells, which are negative for sialyl Lewis X antigen, produced small prostate tumors. The aggressive tumor formation by PC-3-FTIII cells was inhibited by preincubation of the tumor cells with anti-sialyl Lewis X antibody, by the presence of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide but not by control peptide. PC-3-FTIII cells and mock-transfected PC-3 cells exhibited no significant difference in cell numbers when cultured in vitro. Remarkably, PC-3-FTIII adhered to prostatic stromal cells in vitro with higher affinity than mock-transfected PC-3. Such adhesion was inhibited by preincubation of PC-3-FTIII cells with antisialyl Lewis X antibody, by the addition of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide. However, anti-E-selectin, anti-P-selectin or anti-L-selectin antibodies did not inhibit the adhesion of PC-3-FTIII cells to the stromal cells. These results suggest that prostate cancer cells gain aggressiveness through adhesive interaction with prostatic stromal cells by a novel mechanism involving sialyl Lewis X., (Copyright 2003 Wiley-Liss, Inc.)