Gene expression profile in bone metastatic prostate cancer cell line, PC3, following growth in bone marrow conditioned medium (BMCM)
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Diptiman Chanda
PROVIDER: E-GEOD-38714 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:To determine initial genetic changes in the prostate cancer cells following migration to skeleton
2013-12-31 | GSE38714 | GEO
Project description:Tumor microenvironment or stroma has the potency to regulate the behavior of malignant cells. Fibroblast-like cells are abundant in tumor stroma and they are also responsible for the synthesis of many extracellular matrix components. Fibroblast–cancer cell interplay can modify the functions of both cell types. We applied mass spectrometry and proteomics to unveil the matrisome in 3D spheroids formed by DU145 prostate cancer cells, PC3 prostate cancer cells or prostate derived fibroblasts. Similarly DU145/fibroblast and PC3/fibroblast co-culture spheroids were also analyzed. Western Blotting and immunofluorescence were used to confirm the presence of specific proteins in spheroids. Cancer dissemination was studied by utilizing "out of spheroids" migration and invasion assays. In the spheroid model cancer cell–fibroblast interplay caused remarkable changes in extracellular matrix and accelerated the invasion of DU145 cells. Fibroblasts produced structural matrix proteins, growth factors and matrix metalloproteinases. In cancer cell/fibroblast co-cultures basement membrane components, including laminins (3, 5, 2, 3), heparan sulphate proteoglycan (HSPG2 gene product), and collagen XVIII accumulated in a prominent manner when compared to spheroids that contained fibroblasts or cancer cells only. Furthermore, collagen XVIII was intensively processed to different endostatin isoforms by cancer cell derived cathepsin L. To sum up, fibroblasts can promote carcinoma cell dissemination by several different mechanisms. Extracellular matrix and basement membrane proteins provide attachment sites for cell locomotion promoting adhesion receptors. Growth factors and metalloproteinases are known to accelerate cell invasion. Additionally, cancer cell–fibroblast interplay generates biologically active fragments of basement membrane proteins, such as endostatin.
2020-05-04 | PXD016882 | Pride
Project description:Disseminated prostate cancer cells colonize the skeleton to progress into macroscopic lesions only if they successfully adapt to the bone microenvironment. We previously reported that the ability of prostate cancer cells to generate skeletal tumors in animal models correlated with the expression of the alpha-receptor for Platelet-Derived Growth Factor (PDGFRa). In this study we aimed to identify PDGFRa-regulated genes responsible for the acquisition of a bone-metastatic prostate phenotype. We performed genome-wide expression comparative analyses of human prostate cancer cell lines that differ for PDGFRa expression and propensity to establish tumors in the skeleton of animal models. We investigated the genes that were differentially regulated in the highly bone-metastatic PC3-ML cells and their low-metastatic counterpart PC3-N cells, and the genes differentially regulated between PC3-N and PC3-N with overexpression of PDGFRa (PC3NRa). We have previously shown that DU-145 cells lack PDGFRa and fail to survive longer than three days as disseminated tumor cells after homing to the mouse bone marrow. Interestingly, and in contrast to PC3-N cells, the exogenous expression of PDGFRa did not promote metastatic bone-tropism of DU-145 cells in our model. Thus, we examined the genes that were differentially regulated between DU-145 and DU-145(Ra) and excluded them from our candidate genes. Finally, to refine our findings and compensate for PC3 and DU-145 genetic disparity, we performed a comparative analysis of the genes differentially regulated between two bone metastatic single-cell progenies that were derived from PC3-ML cells.
2013-03-30 | GSE43332 | GEO
Project description:Disseminated prostate cancer cells colonize the skeleton to progress into macroscopic lesions only if they successfully adapt to the bone microenvironment. We previously reported that the ability of prostate cancer cells to generate skeletal tumors in animal models correlated with the expression of the alpha-receptor for Platelet-Derived Growth Factor (PDGFRa). In this study we aimed to identify PDGFRa-regulated genes responsible for the acquisition of a bone-metastatic prostate phenotype. We performed genome-wide expression comparative analyses of human prostate cancer cell lines that differ for PDGFRa expression and propensity to establish tumors in the skeleton of animal models. We investigated the genes that were differentially regulated in the highly bone-metastatic PC3-ML cells and their low-metastatic counterpart PC3-N cells, and the genes differentially regulated between PC3-N and PC3-N with overexpression of PDGFRa (PC3NRa). We have previously shown that DU-145 cells lack PDGFRa and fail to survive longer than three days as disseminated tumor cells after homing to the mouse bone marrow. Interestingly, and in contrast to PC3-N cells, the exogenous expression of PDGFRa did not promote metastatic bone-tropism of DU-145 cells in our model. Thus, we examined the genes that were differentially regulated between DU-145 and DU-145(Ra) and excluded them from our candidate genes. Finally, to refine our findings and compensate for PC3 and DU-145 genetic disparity, we performed a comparative analysis of the genes differentially regulated between two bone metastatic single-cell progenies that were derived from PC3-ML cells. Seven human prostate cancer cell lines were analyzed in total for this study. Each cell line was analyzed in duplicate from two different passages in culture.
2013-03-30 | E-GEOD-43332 | biostudies-arrayexpress
Project description:BACKGROUND: Cancer stem-like cells are proposed to sustain solid tumors by virtue of their capacity for self-renewal and differentiation to cells that comprise the bulk of the tumor, and have been identified for a variety of cancers based on characteristic clonal morphologies and patterns of marker gene expression. METHODS: Single cell cloning and spheroid culture studies were used to identify a population of cancer stem-like cells in the androgen-independent human prostate cancer cell line PC3. RESULTS: We demonstrate that, under standard culture conditions, ~10% of PC3 cells form holoclones with cancer stem cell characteristics. These holoclones display high self-renewal capability in spheroid formation assays under low attachment and serum-free culture conditions, retain their holoclone morphology when passaged at high cell density, exhibit moderate drug resistance, and show high tumorigenicity in scid immunodeficient mice. PC3 holoclones readily form spheres, and PC3-derived spheres yield a high percentage of holoclones, further supporting their cancer stem cell-like nature. We identified one gene, FAM65B, whose expression is consistently up regulated in PC3 holoclones compared to paraclones, the major cell morphology in the parental PC3 cell population, and two genes, MFI2 and LEF1, that are consistently down regulated. This molecular profile, FAM65Bhigh/MFI2low/LEF1low, also characterizes spheres generated from parental PC3 cells. The PC3 holoclones did not show significant enriched expression of the putative prostate cancer stem cell markers CD44 and integrin α2β1. PC3 tumors seeded with holoclones showed dramatic down regulation of FAM65B and dramatic up regulation of MFI2 and LEF1, and unexpectedly, a marked increase in tumor vascularity compared to parental PC3 tumors, suggesting a role of cancer stem cells in tumor angiogenesis. CONCLUSIONS: These findings support the proposal that PC3 tumors are sustained by a small number of tumor-initiating cells with stem-like characteristics, including strong self-renewal and pro-angiogenic capability and marked by the expression pattern FAM65Bhigh/MFI2low/LEF1low. These markers may serve as targets for therapies designed to eliminate cancer stem cell populations associated with aggressive, androgen-independent prostate tumors such as PC3. (Mol Cancer. 2010 Dec 29;9:319. doi: 10.1186/1476-4598-9-319; PMID: 21190562; PMCID: PMC3024252).
2013-11-07 | GSE52161 | GEO
Project description:BACKGROUND: Cancer stem-like cells are proposed to sustain solid tumors by virtue of their capacity for self-renewal and differentiation to cells that comprise the bulk of the tumor, and have been identified for a variety of cancers based on characteristic clonal morphologies and patterns of marker gene expression. METHODS: Single cell cloning and spheroid culture studies were used to identify a population of cancer stem-like cells in the androgen-independent human prostate cancer cell line PC3. RESULTS: We demonstrate that, under standard culture conditions, ~10% of PC3 cells form holoclones with cancer stem cell characteristics. These holoclones display high self-renewal capability in spheroid formation assays under low attachment and serum-free culture conditions, retain their holoclone morphology when passaged at high cell density, exhibit moderate drug resistance, and show high tumorigenicity in scid immunodeficient mice. PC3 holoclones readily form spheres, and PC3-derived spheres yield a high percentage of holoclones, further supporting their cancer stem cell-like nature. We identified one gene, FAM65B, whose expression is consistently up regulated in PC3 holoclones compared to paraclones, the major cell morphology in the parental PC3 cell population, and two genes, MFI2 and LEF1, that are consistently down regulated. This molecular profile, FAM65Bhigh/MFI2low/LEF1low, also characterizes spheres generated from parental PC3 cells. The PC3 holoclones did not show significant enriched expression of the putative prostate cancer stem cell markers CD44 and integrin M-NM-12M-NM-21. PC3 tumors seeded with holoclones showed dramatic down regulation of FAM65B and dramatic up regulation of MFI2 and LEF1, and unexpectedly, a marked increase in tumor vascularity compared to parental PC3 tumors, suggesting a role of cancer stem cells in tumor angiogenesis. CONCLUSIONS: These findings support the proposal that PC3 tumors are sustained by a small number of tumor-initiating cells with stem-like characteristics, including strong self-renewal and pro-angiogenic capability and marked by the expression pattern FAM65Bhigh/MFI2low/LEF1low. These markers may serve as targets for therapies designed to eliminate cancer stem cell populations associated with aggressive, androgen-independent prostate tumors such as PC3. (Mol Cancer. 2010 Dec 29;9:319. doi: 10.1186/1476-4598-9-319; PMID: 21190562; PMCID: PMC3024252). Four PC3 cell-derived holoclones, selected based on their clear and unambiguous holoclone morphology and designated holoclones 2H10, 2G7, 1A8 and 5A2, were used for global transcriptome/microarray analysis in direct comparison to parental PC3 cells. Total RNA was prepared from each of four sequential cell passages for each PC3-derived holoclone, and from four passages of parental PC3 cells, 48 h after seeding the cells at 100,000 cells per well of a 6-well plate. For each sample (holoclones or parental PC3 cells), a pool of RNA was prepared by combining equal amounts of RNA from each passage to minimize the effects of passage number and inter-sample variability on gene expression profiles. All RNAs had an RNA integrity number >8.0, determined using an Agilent Bioanalyzer 2100 instrument. cDNAs transcribed from pools of RNA for each holoclone, and for parental PC3 cells, were labeled with Alexa 647 or Alexa 555 dyes in a fluorescent reverse pair (dye swap) design for competitive hybridization to Agilent Whole Human Genome Microarrays.
2013-11-07 | E-GEOD-52161 | biostudies-arrayexpress
Project description:PC3 cells were grown in 10% DMEM with FBS and treated with vehicle (DMSO), 100 nM rapamycin, or 100 nM DL001 for 24 hours
2019-03-20 | MSV000083602 | MassIVE
Project description:It is aimed to reveal overall trancriptional change in prostate cancer PC3 cells after ectopic expression of miR-145 Pre-mir-145 transfected PC3 cells were collected at 8, 16 and 24 hours after transfection and control untrasfected PC3 cells were used.
2014-06-15 | E-GEOD-58295 | biostudies-arrayexpress