Search

Ras homolog gene family, member A (RhoA) has been reported as essential to the invasion process and aggressiveness of numerous cancers. However, there are only sparse data on the expression and activity of RhoA in clinically localised prostate cancer. In numerous cancers, tumour cells at the invasive front demonstrate more aggressive behaviour in comparison with the cells in the central regions. In the present study, the expression and activity of RhoA was evaluated in 34 paraffin-embedded and 20 frozen prostate tissue specimens obtained from 45 patients treated with radical prostatectomy for clinically localised cancer. The expression patterns of RhoA were assessed by immunohistochemical staining and western blotting. Additional comparisons were performed between the tumour centre, tumour front and distant peritumoural tissue. RhoA activity was assessed by G-LISA. Associations between RhoA expression and the clinical features and outcome of the patients were also analysed. The present study found an increasing gradient of expression from the centre to the periphery of index tumour foci. RhoA expression was significantly increased at the tumour front compared to the tumour centre, which was determined using immunohistochemistry (P=0.001). Increased RhoA expression was associated with poor tumour differentiation in the tumour front (P=0.044) and tumour centre (P=0.039). Subsequent to a median follow-up period of 52 months, the rate of prostate-specific antigen (PSA) relapse was increased in patients with higher RhoA expression at the tumour front when compared with patients with lower RhoA expression (62.5 vs. 35.0%), although the difference was not significant (P=0.09). There was no association between RhoA expression and the PSA level or pathological stage in the present study. In conclusion, RhoA expression was increased at the tumour front and was associated with poor tumour differentiation in the tumour front and tumour centre, indicating the potential role of RhoA in prostate cancer. RhoA expression may also act as a prognostic factor in prostate cancer. The present data provide a foundation for novel therapeutic approaches by targeting RhoA in prostate cancer. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) remains a major cause of mortality among males in western countries, with little change in mortality rates observed over the past 25 years. Despite recent advances in therapy, treatment options for metastatic castration-resistant disease remain limited. In terms of chemotherapy, only the combination of docetaxel and prednisone has been shown to improve survival in these patients, but duration of response to therapy is short. There is a continuing unmet need for new systemic interventions that act either alone or synergistically with chemotherapy in patients with progressive PCa. Angiogenesis plays a critical role in tumor growth and metastasis in PCa. Several strategies have been used to target angiogenesis; however, it is becoming increasingly apparent that current anti-angiogenic therapies frequently achieve only modest effects in clinical settings. The RhoA/Rho kinase (ROCK) pathway plays a crucial role in the process of angiogenesis in PCa, and studies have demonstrated that ROCK inhibitors decrease VEGF-induced angiogenesis and tumor cell growth. However, further research is required to fully elucidate the molecular mechanisms involved in this pathway, and the potential value of modulating these mechanisms in the treatment of PCa. This study reviews the current understanding of the role of the RhoA/ROCK pathway in the process of angiogenesis in PCa, and the potential of this pathway as a therapeutic target in the future. [ABSTRACT FROM AUTHOR]