Early human prostate adenocarcinomas harbor androgen-independent cancer cells.

Although blockade of androgen receptor (AR) signaling represents the main treatment for advanced prostate cancer (PrCa), many patients progress to a lethal phenotype of "Castration-Resistant" prostate cancer (CR-PrCa). With the hypothesis that early PrCa may harbor a population of androgen-unresponsive cancer cells as precursors to CR-recurrent disease, we undertook the propagation of androgen-independent cells from PrCa-prostatectomy samples of early, localized (Stage-I) cases. A collection of 120 surgical specimens from prostatectomy cases was established, among which 54 were adenocarcinomas. Hormone-free cell culture conditions were developed allowing routine propagation of cells expressing prostate basal cell markers and stem/progenitor cell markers, and which proliferated as spheres/spheroids in suspension cultures. Colonies of androgen-independent epithelial cells grew out from 30/43 (70%) of the adenocarcinoma cases studied in detail. Fluorescence microscopy and flow cytometry showed that CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin α2ß1, SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH). All 30 CR-PrCa cell cultures were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of 22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in intact and castrated SCID mice, generating histologically typical locally-invasive human PrCa or undifferentiated cancers, respectively, in 6-8 weeks. Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC) directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa.

Nanotoxicity of iron oxide nanoparticle internalization in growing neurons.

Magnetic nanoparticles (MNPs) have shown great promise for use as tools in a wide variety of biomedical applications, some of which require the delivery of large numbers of MNPs onto or into the cells of interest. Here we develop a quantifiable model cell system and show that intracellular delivery of even moderate levels of iron oxide (Fe(2)O(3)) nanoparticles may adversely affect cell function. More specifically, we show that exposure to increasing concentrations of anionic MNPs, from 0.15 to 15 mm of iron, results in a dose-dependent diminishing viability and capacity of PC12 cells to extend neurites in response to their putative biological cue, i.e. nerve growth factor. The cytotoxicity results of biomaterials in our model system imply that more study into the acute and long-term effects of cellular Fe(2)O(3) internalization is both warranted and necessary.

Significantly accelerated osteoblast cell growth on aligned TiO2 nanotubes.

Vertically aligned yet laterally spaced nanoscale TiO2 nanotubes have been grown on Ti by anodization, and the growth of MC3T3-E1 osteoblast cells on such nanotubes has been investigated. The adhesion/propagation of the osteoblast is substantially improved by the topography of the TiO2 nanotubes with the filopodia of growing cells actually going into the nanotube pores, producing an interlocked cell structure. The presence of the nanotube structure induced a significant acceleration in the growth rate of osteoblast cells by as much as approximately 300-400%.

Growth of nano-scale hydroxyapatite using chemically treated titanium oxide nanotubes.

A vertically aligned nanotube array of titanium oxide was fabricated on the surface of titanium substrate by anodization. The nanotubes were then treated with NaOH solution to make them bioactive, and to induce growth of hydroxyapatite (bone-like calcium phosphate) in a simulated body fluid. It is shown that the presence of TiO2 nanotubes induces the growth of a "nano-inspired nanostructure", i.e., extremely fine-scale (approximately 8 nm feature) nanofibers of bioactive sodium titanate structure on the top edge of the approximately 15 nm thick nanotube wall. During the subsequent in-vitro immersion in a simulated body fluid, the nano-scale sodium titanate, in turn, induced the nucleation and growth nano-dimensioned hydroxyapatite (HAp) phase. The kinetics of HAp formation is significantly accelerated by the presence of the nanostructures. Such TiO2 nanotube arrays and associated nanostructures can be useful as a well-adhered bioactive surface layer on Ti implant metals for orthopaedic and dental implants, as well as for photocatalysts and other sensor applications.