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3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
ST3Gal.I sialyltransferase relevance in bladder cancer tissues and cell lines
Paula A Videira1, Manuela Correia, Nadia Malagolini
1CEDOC, Departamento de Imunologia, Faculdade de Ciências Médicas, FCM, Universidade Nova de Lisboa, Lisboa, Portugal. paula.videira@fcm.unl.pt
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.
Insights
ST3Gal.I is key in sialylating the T antigen in bladder cancer. Its overexpression may signal early cancer development and predict progression, aiding in prognosis.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- The sialyl-T antigen is a tumor marker linked to poor bladder cancer prognosis.
- Altered expression of sialyltransferases contributes to sialyl-T antigen formation.
- Limited information exists on sialyltransferases involved in T antigen sialylation in bladder cancer.
Purpose of the Study:
- To investigate the regulation of sialyltransferases responsible for T antigen sialylation in bladder cancer progression.
- To determine the specific role of ST3Gal.I, ST3Gal.II, and ST3Gal.IV in bladder cancer.
Main Methods:
- Real-time PCR was used to quantify ST3Gal.I, ST3Gal.II, and ST3Gal.IV mRNA levels in bladder tissues and cell lines.
- Sialyl-T antigen expression was assessed using dot blot and flow cytometry.
- Sialyltransferase activity was measured in bladder cancer cell lines.
Main Results:
- ST3Gal.I mRNA levels were significantly elevated in nonmuscle-invasive and muscle-invasive bladder cancers compared to normal urothelium.
- A strong correlation was found between ST3Gal.I mRNA levels, sialyltransferase activity, and sialyl-T antigen expression in cell lines.
- Sialyl-T antigens were detected in patient tumors and urothelium, though not strongly correlated with mRNA levels.
Conclusions:
- ST3Gal.I is the primary enzyme responsible for T antigen sialylation in bladder cancer.
- ST3Gal.I overexpression appears to be an early event in bladder oncogenesis.
- ST3Gal.I can be a valuable biomarker for predicting bladder cancer progression and recurrence.
