CXCL13 mediates prostate cancer cell proliferation through JNK signalling and invasion through ERK activation.

OBJECTIVES: The focus of this study was to determine the dedicator of cytokinesis 2 (DOCK2), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase-1 (JNK) and Akt signals involved in CXCL13-mediated prostate cancer (PCa) cell invasion and proliferation. MATERIALS AND METHODS: Androgen-sensitive (LNCaP), hormone-refractory (PC3) cells and normal cells (RWPE-1) were used to determine CXCL13-mediated PCa cell invasion and proliferation. Immuno-blotting, fast activated cell-based (FACE) ELISA, caspase activity, cell invasion and proliferation assays were performed to ascertain some of the signalling events involved in PCa cell proliferation and invasion. RESULTS: Unlike androgen-sensitive LNCaP cells, we report for the first time that the hormone-refractory cell line, PC3, expresses DOCK2. CXCL13-mediated LNCaP and PC3 cell invasion was regulated by Akt and ERK1/2 activation in a DOCK2-independent fashion. CXCL13 also promoted LNCaP cell proliferation in a JNK-dependent fashion even in the absence of DOCK2. In contrast, CXCL13 induced PC3 cell proliferation through JNK activation, which required DOCK2. CONCLUSIONS: Our results show CXCL13-mediated PCa cell invasion requires Akt and ERK1/2 activation and suggests a new role for DOCK2 in proliferation of hormone-refractory CXCR5-positive PCa cells.

Viscocanalostomy versus trabeculotomy ab externo in primary congenital glaucoma: 1-year follow-up of a prospective controlled pilot study.

AIM: To study the effectiveness of viscocanalostomy in patients with primary congenital glaucoma of the isolated trabecular dysgenesis category and compare it with trabeculotomy ab externo. METHODS: Eight patients with bilateral primary congenital glaucoma were enrolled in the study. After establishing the diagnosis, the more severely affected eye was randomly selected to undergo either trabeculotomy ab externo or viscocanalostomy, whereas the second eye underwent the other surgery 2 weeks after the first. The patients were examined on day 1, week 1, week 4 and thereafter every 4 weeks. Intraocular pressure (IOP) and corneal diameter measurements were obtained at week 1, month 6 and at the last reported follow-up. The paired-sample's Student's t test was applied for statistical analysis. RESULTS: The mean (standard deviation (SD)) follow-up period was 12.5 (1.86) months. Preoperative IOP of eyes undergoing trabeculotomy (34.0 (2.6) mm Hg) and that of eyes undergoing viscocanalostomy (32.3 (4.1) mm Hg) showed no significant difference (p>0.1). A drop in IOP was noted in both groups at week 1, month 6 and at the last follow-up visit (p<0.001). Similarly, a decrease in the postoperative vertical and horizontal corneal diameters was noted in the two study groups. CONCLUSION: Viscocanalostomy proved to be as effective as trabeculotomy ab externo in lowering IOP. Moreover, it is likely to be a good surgical alternative with a higher long-term success rate in eyes with more aggressive disease.