Androgen-Regulated Transcriptional Control of Sialyltransferases in Prostate Cancer Cells

The expression of gangliosides is often associated with cancer progression. Sialyltransferases have received much attention in terms of their relationship with cancer because they modulate the expression of gangliosides. We previously demonstrated that GD1a production was high in castration-resistant prostate cancer cell lines, PC3 and DU145, mainly due to their high expression of β-galactoside α2,3-sialyltransferase (ST3Gal) II (not ST3Gal I), and the expression of both ST3Gals was regulated by NF-κB, mainly by RelB. We herein demonstrate that GD1a was produced in abundance in cancerous tissue samples from human patients with hormone-sensitive prostate cancers as well as castration-resistant prostate cancers. The expression of ST3Gal II was constitutively activated in castration-resistant prostate cancer cell lines, PC3 and DU145, because of the hypomethylation of CpG island in its promoter. However, in androgen-depleted LNCap cells, a hormone-sensitive prostate cancer cell line, the expression of ST3Gal II was silenced because of the hypermethylation of the promoter region. The expression of ST3Gal II in LNCap cells increased with testosterone treatment because of the demethylation of the CpG sites. This testosterone-dependent ST3Gal II expression was suppressed by RelB siRNA, indicating that RelB activated ST3Gal II transcription in the testosterone-induced demethylated promoter. Therefore, in hormone-sensitive prostate cancers, the production of GD1a may be regulated by androgen. This is the first report indicating that the expression of a sialyltransferase is transcriptionally regulated by androgen-dependent demethylation of the CpG sites in its gene promoter

Development of Subcutaneous SSEA3- or SSEA4-Positive Cell Capture Device

Securing high-quality cell sources is important in regenerative medicine. In this study, we developed a device that can accumulate autologous stem cells in the body. When small wire-assembled molds were embedded in the dorsal subcutaneous pouches of beagles for several weeks, collagen-based tissues with minimal inflammation formed inside the molds. At 3 weeks of embedding, the outer areas of the tissues were composed of immature type III collagen with large amounts of cells expressing SSEA3 or SSEA4 markers, in addition to growth factors such as HGF or VEGF. When separated from the tissues by collagenase treatment, approximately four million cells with a proportion of 70% CD90-positive and 20% SSEA3- or SSEA4-positive cells were recovered from the single mold. The cells could differentiate into bone or cartilage cells. The obtained cell-containing tissues are expected to have potential as therapeutic materials or cell sources in regenerative medicine

Non-Euclidean Stress-Free Configuration of Arteries Accounting for Curl of Axial Strips Sectioned From Vessels

It is well known that arteries are subject to residual stress. In earlier studies, the residual stress in the arterial ring relieved by a radial cut was considered in stress analysis. However, it has been found that axial strips sectioned from arteries also curled into arcs, showing that the axial residual stresses were relieved from the arterial walls. The combined relief of circumferential and axial residual stresses must be considered to accurately analyze stress and strain distributions under physiological loading conditions. In the present study, a mathematical model of a stress-free configuration of artery was proposed using Riemannian geometry. Stress analysis for arterial walls under unloaded and physiologically loaded conditions was performed using exponential strain energy functions for porcine and human common carotid arteries. In the porcine artery, the circumferential stress distribution under physiological loading became uniform compared with that without axial residual strain, whereas a gradient of axial stress distribution increased through the wall thickness. This behavior showed almost the same pattern that was observed in a recent study in which approximate analysis accounting for circumferential and axial residual strains was performed, whereas the circumferential and axial stresses increased from the inner surface to the outer surface under a physiological condition in the human common carotid artery of a two-layer model based on data of other recent studies. In both analyses, Riemannian geometry was appropriate to define the stress-free configurations of the arterial walls with both circumferential and axial residual strains