However, the factors regulating these effects are not completely understood

migrated 62% faster into the wound area than the control cells after 36 h. In comparison, PLL, PLO and FN caused LNCaP cells to migrate slower than the control, displaying a reduction of wound density by 15%, 33% and 20% grown under these conditions respectively. Notably, LNCaP cells displayed a doubling time around 36 h, as observed in the RTCA experiments, suggesting that the observed effects on the wound density were caused predominantly by cell migration and not proliferation. PLL sensitizes LNCaP cells for the HMGCR inhibitor simvastatin Previous studies have shown that the pre-coating with ECM components can affect the sensitivity of cells to various drugs. For instance, LAM and FN have been Debio 1347 web reported to increase resistance to ionizing radiation and to PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19689277 the cytotoxic drug Ukrain in human tumor and normal cells in vitro. Furthermore, it was reported that adherence to a FN substrate induced cholesterol synthesis through activation of HMGCR and also increased fatty acid synthesis in human fibroblasts and rat hepatoma cells, while a PLL substrate or FN in solution had no effect on these pathways. Hence, the effect of the coating reagents PLL, PLO and FN on the sensitivity of LNCaP cells to the HMGCR inhibitor simvastatin was investigated by RTCA, and the IC50 was calculated for treatment periods of 24 h, 48 h, and 72 h. LAM and COL effects were not analyzed because these coating reagents had adverse effects on LNCaP cell-surface adherence and caused cell aggregation. While the IC50 for simvastatin was relatively similar among the four coating conditions at 24 h, PLL increased the sensitivity of LNCaP cells to the HMGCR inhibitor by two-fold after 48 h of treatment when compared to control. At 72 h, LNCaP cells grown on a PLL substrate displayed a three-fold lower IC50. Similarly, PLO and FN increased the sensitivity of LNCaP cells to simvastatin by two-fold relative to the control at 72 h. However, it has been observed that PLO, PLL and FN reduced the cell viability by one third at 96 h. Hence, the sensitization of LNCaP cells by PLO and FN to simvastatin might be actually the effect of these coatings on cell viability. In this case, only PLL may 7 Differential Effects of Coating Substrates on Prostate Cancer Cell significantly sensitize LNCaP cells for the HMGCR inhibitor simvastatin in a time-dependent manner. Androgen responsiveness and AR signaling were in general not affected by the coating conditions In the healthy human adult prostate epithelium, AR expression and cell PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19692147 adhesion to the substratum occur in separate cell layers, namely in luminal and basal cells. Hence, the pathways of AR signaling and cell adhesion are unlikely to interact directly. During the development of prostate cancer, malignant luminal epithelial cells change from cell-cell adhesion to cell-substratum adhesion, and signals from cell adhesion and AR are co-expressed. The LNCaP cell line is an important model system to study androgen receptor -mediated signaling in prostate cancer. It was recently shown that changes to cell-cell contacts and the extracellular matrix altered the response of LNCaP cells to androgens. Hence, it was important to investigate if the coating reagents FN, PLL and PLO, which increased LNCaP adherence, affected AR signaling in this model system. To address this issue, the expression of genes regulated by androgens was examined by qRT-PCR. As shown in 8 Differential Effects of Coating Substrates on Prostate Cancer Cell genes derived fro