Proepithelin is an autocrine growth factor for bladder cancer

Abstract

The growth factor proepithelin functions as an important regulator of proliferation and motility. Proepithelin is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian and renal cancer, as well as glioblastomas. Using recombinant proepithelin on 5637 transitional cell carcinoma-derived cells, we have shown previously that proepithelin plays a critical role in bladder cancer by promoting motility of bladder cancer cells. In this study, we used the ONCOMINE database and gene microarray analysis tool to analyze proepithelin expression in several bladder cancer microarray studies. We found a statistically significant increase in proepithelin messenger RNA expression in bladder cancers vis-à-vis non-neoplastic tissues, and this was associated with pathologic and prognostic parameters. Targeted downregulation of proepithelin in T24 transitional carcinoma cells with small hairpin RNA inhibited both Akt and mitogen-activated protein kinase pathways, severely reduced the ability of T24 cells to proliferate in the absence of serum and inhibited migration, invasion and wound healing. In support of these in vitro results, we discovered that proepithelin expression was significantly upregulated in invasive bladder cancer tissues compared with normal urothelium. In addition, proepithelin was secreted in the urine, where it was detectable by immunoblotting and enzyme-linked immunosorbent assay. Collectively, these results support the hypothesis that proepithelin may play a critical role as an autocrine growth factor in the establishment and progression of bladder cancer and suggest that proepithelin may prove a novel biomarker for the diagnosis and prognosis of bladder neoplasms.

Epithelial–mesenchymal transition in malignant mesothelioma

“…After 24 h, the cells in the upper chamber were removed, whereas the cells that migrated to the lower chamber were counted under the microscope after fixing and staining in Coomassie blue solution, as described. 34,35 …”

“…34,35 Briefly, cells were starved of serum for 24 h, then seeded in triplicate (10 3 in 200 ml) in Boyden chambers (upper chamber) (BD Biosciences). Lower chambers contained 500 ml of SFM or 500 ml of medium supplemented with 10% fetal bovine serum.…”

Decorin Antagonizes IGF Receptor I (IGF-IR) Function by Interfering with IGF-IR Activity and Attenuating Downstream Signaling

“…Tissues-Immunohistochemical analysis of IGF-IR levels in bladder tissues was performed as previously described (19,49). Formalin-fixed paraffin-embedded sections from 20 high grade and 20 low grade urothelial cell carcinomas and adjacent normal tissues were obtained from the Pathology Tissue Bank of Thomas Jefferson University.…”

“…All of the images were then analyzed using Image J and Adobe Photoshop CS3 (Adobe Systems, San Jose, CA) software. Migration, Wound, and Invasion Assays-Migration experiments were performed using HTS FluoroBloks TM inserts (Becton Dickinson) as previously described (19,49,53). The membranes were mounted on a slide, and migrated cells were counted and photographed with a Zeiss Axiovert 200M cell live microscope at the Kimmel Cancer Center Bioimaging Facility.…”

Expression Pattern of Progranulin in the Human Placenta and Its Effect on Cell Proliferation in the Choriocarcinoma Cell Line BeWo

“…In adults, progranulin was also measured in urine [17]. This suggests that the amniotic fluid levels would be of fetal origin.…”