Project description:Disseminated epithelial cells can be isolated from the bone marrow of a far greater frac-tion of prostate-cancer patients than the fraction of patients who progress to metastatic disease. To provide a better understanding of these cells, we have characterized their genomic altera-tions. We first present an array comparative genomic hybridization method capable of detecting genomic changes in the small number of disseminated cells (10-20) that can typically be ob-tained from bone-marrow aspirates of prostate-cancer patients. We show multiple regions of copy-number change, including alterations common in prostate cancer, such as 8p loss, 8q gain, and gain encompassing the androgen-receptor gene on Xq, in the disseminated cell pools from 11 metastatic patients. We found fewer and less striking genomic alterations in the 48 pools of disseminated cells from patients with organ-confined disease. However, we identify changes shared by these samples with their corresponding primary tumors and prostate-cancer altera-tions reported in the literature, evidence that these cells, like those in advanced disease, are disseminated tumor cells (DTCs). We also demonstrate that DTCs from patients with advanced and localized disease share several abnormalities, including losses containing cell-adhesion genes and alterations reported to associate with progressive disease. These shared alterations might confer the capability to disseminate or establish secondary disease. Overall, the spectrum of genomic deviations is evidence for metastatic capacity in advanced-disease DTCs and varia-tion in that capacity in DTCs from localized disease. Our analysis lays the foundation for eluci-dation of the relationship between DTC genomic alterations and progressive prostate cancer. Keywords: array comparative genomic hybridization, prostate cancer, disseminated cells
Project description:In this study we performed transcriptional profiling of transurethral resections of hormone resistant prostate cancer and compared it with benign prostatic hyperplasia (BPH), untreated localized prostate cancer and hormone sensitive prostate cancer. Experiment Overall Design: Each sample (= Array) is derived from a different patient with the following subsequent disease states: 3x BPH, 7x localized prostate cancer samples, 2 horomone sensitive prostate cancer samples, one locally advanced prostate cancer, 4x hormone resistant prostate cancer early stage and 3x hormone resistant prostate cancer late stage. Experiment Overall Design: Platform was Affymetrix
Project description:Advanced prostate cancer is a highly heterogenous disease with few in vitro models. We report generation of seven novel 3D organoid lines of patient-derived prostate cancer. We determine the copy number alterations of these lines using array CGH. They contain may classic alterations of prostate cancer such as lost of the short arm of chromosome 8 and gain of the long arm of chromosome 8. In addition, we found homozygous deleteion of tumor suppressor PTEN and CHD1 as well as the TMPRSS2-ERG interstitial deletion. Prostate cancer organoid lines, ~2 months after in vitro propagation, were used for profiling on Agilent 1M aCGH arrays per manufacturer's instructions. A pooled reference normal DNA was used as the reference.
Project description:An integrative analysis of this compendium of proteomic alterations and transcriptomic data was performed revealing only 48-64% concordance between protein and transcript levels. Importantly, differential proteomic alterations between metastatic and clinically localized prostate cancer that mapped concordantly to gene transcripts served as predictors of clinical outcome in prostate cancer as well as other solid tumors. Keywords: prostate cancer progression 13 individual benign prostate, primary and metastatic prostate cancer samples and 6 pooled samples from benign,primary or metastatic prostate cancer tissues.
Project description:Prostate cancer is a unique disease from a metabolic perspective. Early stage localized prostate cancer does not typically display increased aerobic glycolysis (the Warburg effect), as seen in other malignancies. However, increasing evidence suggests that advanced prostate cancer exhibits the Warburg effect and displays high glucose uptake. We describe here that trans-gnetin H (TGH), a naturally-occurring resveratrol trimer extracted from Paeonia suffruticosa, displays significant anti-cancer effects in advanced prostate cancer cells xenografted PC-3 cells in vivo.TGH perturbs energy metabolism by blocking the availability of glucose and inducing profound metabolic and transcriptomic changes in prostate cancer cells as demonstrated by RNA-seq. C-MYC, a known driver oncogene in prostate cancer, is downregulated in TGH-treated cells. Our studies demonstrate the feasibility of targeting aerobic glucose metabolism in advanced prostate cancer and identify TGH as a potential therapeutic candidate.