ST3Gal.I sialyltransferase relevance in bladder cancer tissues and cell lines.

BACKGROUND: The T antigen is a tumor-associated structure whose sialylated form (the sialyl-T antigen) involves the altered expression of sialyltransferases and has been related with worse prognosis. Since little or no information is available on this subject, we investigated the regulation of the sialyltransferases, able to sialylate the T antigen, in bladder cancer progression. METHODS: Matched samples of urothelium and tumor tissue, and four bladder cancer cell lines were screened for: ST3Gal.I, ST3Gal.II and ST3Gal.IV mRNA level by real-time PCR. Sialyl-T antigen was detected by dot blot and flow cytometry using peanut lectin. Sialyltransferase activity was measured against the T antigen in the cell lines. RESULTS: In nonmuscle-invasive bladder cancers, ST3Gal.I mRNA levels were significantly higher than corresponding urothelium (p < 0.001) and this increase was twice more pronounced in cancers with tendency for recurrence. In muscle-invasive cancers and matching urothelium, ST3Gal.I mRNA levels were as elevated as nonmuscle-invasive cancers. Both non-malignant bladder tumors and corresponding urothelium showed ST3Gal.I mRNA levels lower than all the other specimen groups. A good correlation was observed in bladder cancer cell lines between the ST3Gal.I mRNA level, the ST activity (r = 0.99; p = 0.001) and sialyl-T antigen expression, demonstrating that sialylation of T antigen is attributable to ST3Gal.I. The expression of sialyl-T antigens was found in patients' bladder tumors and urothelium, although without a marked relationship with mRNA level. The two ST3Gal.I transcript variants were also equally expressed, independently of cell phenotype or malignancy. CONCLUSION: ST3Gal.I plays the major role in the sialylation of the T antigen in bladder cancer. The overexpression of ST3Gal.I seems to be part of the initial oncogenic transformation of bladder and can be considered when predicting cancer progression and recurrence.

Efficacy of bacille Calmette-Guérin immunotherapy predicted by expression of antigen-presenting molecules and chemokines.

OBJECTIVES: To ascertain the role and prognostic value of antigen-presenting molecules and chemokines in the prophylactic effect of intravesical bacille Calmette-Guérin (BCG) in tumor recurrence. We compared its gene expression in urothelium biopsy and tumor specimens from patients who had undergone BCG immunotherapy. METHODS: Patients with nonmuscle-invasive bladder cancer were divided into 3 groups, according to the cancer recurrence status: group 1, primary cancer without recurrence for a minimal period of 12 months; group 2, primary cancer with subsequent recurrence; and group 3, recurrent cancer at study entry. From each patient, cancerous bladder tissue and biopsy specimens of the urothelium (before and 3 months after transurethral resection of the bladder) were collected. The RNA levels of the antigen-presenting molecules CD1a, CD1b, CD1c, CD1d, CD1e, and major histocompatability complex-I, class I (MHC-I) and the chemokines macrophage inflammatory protein-1alpha, monocyte chemoattractant protein-1 and -2, interferon-inducible protein 10 kD (IP10), and monokine induced by gamma-interferon (MIG) were evaluated using real-time polymerase chain reaction on all samples. RESULTS: Generally, BCG treatment increased the urothelium expression of antigen-presenting molecules and chemokines. However, the differences for CD1a (P = .005), CD1b (P < .000), CD1c (P = .03), CD1e (P = .007), MHC-I (P < .000), MIG (P < .0001), and IP10 (P < .0001) were significantly superior in the BCG-treated urothelium of group 1 compared with the other groups. Tumor tissue from group 1 also had increased expression of MHC-I (P = .04) and contrasted with tumor tissue from group 3 with decreased expression of CD1c (P = .007) and CD1e (P = .02). CONCLUSIONS: Patients without recurrence had greater increased urothelium expression of antigen-presenting molecules and chemokines after BCG treatment. These parameters might, therefore, serve to predict and monitor the efficacy of BCG immunotherapy.