A comparative study of glycoproteomes in androgen-sensitive and -independent prostate cancer cell lines

Anna Drabik,Dorota Ciołczyk-Wierzbicka,Anna Bodzoń-Kułakowska,Piotr Laidler,Piotr Suder,Joanna Dulińska-Litewka,Jerzy Silberring

doi:10.1007/s11010-013-1857-6

Abstract

Prostate cancer is one of the most common malignancies in men and is predicted to be the second leading cause of cancer-related deaths. After 6–18 months, hormone ablation treatment results in androgen-independent growth of cancer cells, metastasis and progression. The mechanism of androgen-independent growth of prostatic carcinoma cells is still unknown. Identification of factors that facilitate the transition from androgen-dependent to independent states is crucial in designing future diagnostics and medication strategies. To understand the biochemical meaning of hormone dependency deprivation, glycoproteins enriched profiles were compared between DU145 (hormone non-responding) and LNCaP (hormone responding) prostate cancer cells. These results allow for anticipation on the important role of glycosylation in malignant transformation. Both Tn antigen and complex antennary N-oligosaccharides were recognized. Their occurrence might be involved in the development and progression of tumor, and failure of hormone ablation therapy. Among identified proteins in androgen-sensitive cells nucleolin (P19338) was found that is widely described as apoptosis inhibitor, and also transporter of molecules from the membrane to the cytoplasm or nucleus. In addition, 14-3-3 protein family (P27348, P31946, P61981, P63104, P62258, Q04917, and P31947) was investigated across available databases as it forms stable complexes with glycoproteins. Our studies indicate that isoforms: sigma and eta were found in androgen-dependent prostate cancer cells, while other isoforms were present in androgen non-responding cells. 14-3-3 binding partners are involved in cancer pathogenesis. These findings may contribute to a better understanding of prostate cancer tumorigenesis and to a more efficient prognosis and individual therapy in a future. However, it still remains to be revealed how important those changes are for androgen dependency loss in prostate cancer patients carried out on clinically relevant populations.

Highlights

Our studies indicate that isoforms: sigma and eta were found in androgen-dependent prostate cancer cells, while other isoforms were present in androgen non-responding cells. 14-3-3 binding partners are involved in cancer pathogenesis
Patients with advanced prostate cancer (PCa) initially benefit from androgen ablation therapy, which leads to the temporary tumor remission due to apoptosis of the androgen-sensitive tumor cells [1]
The rationale to focus on glycoproteome is based on the fact that 30 of 38 proteins on the list of biomarkers, proteins involved in disease formation, currently used in clinical diagnostic are known to be glycosylated [2]

Summary

Introduction

Patients with advanced prostate cancer (PCa) initially benefit from androgen ablation therapy, which leads to the temporary tumor remission due to apoptosis of the androgen-sensitive tumor cells [1]. We revealed lectin-enriched proteome changes in the androgen dependency loss between androgen-responding and androgennonresponding prostate cancer cell lines. The site(s) of protein glycosylation and the structure of the oligosaccharides are altered during initiation or progression of the disease; we have focused on analysis of glycosylated subproteome for the reason that affinity reagents reduce sample complexity, and enrich reliability of the results in biologically and clinically important information.

Results

Conclusion