N-octanoyl dopamine (NOD), but not dopamine dose dependently induces the UPR. This was also found for other synthetic N-Acyl dopamine derivates (NADD). Induction of the UPR was dependent on the redox activity of NADD and was not caused by selective activation of a particular UPR sensor. UPR induction did not result in cell apoptosis, yet NOD strongly impaired cell proliferation by attenuation of cells in the S-G2/M phase. Long-term treatment of HUVEC with low NOD concentration showed decreased intracellular ATP concentration paralleled with activation of AMPK. These cells were significantly more resistant to cold inflicted injury.
N-octanoyl dopamine treatment of endothelial cells induces the unfolded protein response and results in hypometabolism and tolerance to hypothermia.
Cell line, Treatment
View SamplesPrimary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type, or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.
Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.
Specimen part
View SamplesMetastasis depends on the ability of tumor cells to establish a relationship with the newly seeded host tissue that is conducive to their survival and proliferation. Recent evidence suggests that tumor cells regulate their own dissemination by preparing permissive metastatic niches within host tissues. However, the factors that are implicated in rendering tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display highly aggressive behaviour and early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. We show that during murine gestation, both the rate and degree of metastatic tumor growth are enhanced irrespective of tumor type and that decreased natural killer (NK) cell activity is responsible for the observed increase in experimental metastasis. We identify gene expression changes in pregnant mouse lung and liver that bear striking similarity with reported pre-metastatic niche signatures and several of the up-regulated genes are indicative of myeloid-cell infiltration. We provide evidence, that CD11b+ Gr-1+ myeloid-derived suppressor cells accumulate in pregnant mice and exert an inhibitory effect on NK cell activity, thereby enhancing metastatic tumor growth. MDSC have never been evoked in the context of pregnancy and our observations suggest that they may represent a further shared mechanism of immune suppression occurring during gestation and tumor growth.
Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.
Sex, Specimen part
View SamplesThese gene expression microarrays were performed as part of a project aiming to integrate quantitative proteomic, gene expression and epigenetic data from the childhood brain tumor medulloblastoma.
Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.
Sex, Specimen part
View SamplesExpression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not -catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking -catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation.
The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.
Cell line
View SamplesLung cancer is a highly malignant tumor and the majority of cancer-related deaths are due to metastasis. The tumor microenvironment (TME) plays a fundamental role in the metastatic spread of tumor cells. Among other stromal cells, mesenchymal stem cells (MSCs) are known to be present within the TME and to be involved in cancer progression. However the majority of previous studies have been performed on bone marrow-derived MSCs. To investigate the role of the TME on the pulmonary MSC phenotype, we compared the expression profile of paired MSCs isolated from lung tumor (T-) and normal adjacent tissues (N-) from lung carcinoma patients.
Reciprocal modulation of mesenchymal stem cells and tumor cells promotes lung cancer metastasis.
Specimen part, Disease stage, Subject
View SamplesCurrent prophylactic and therapeutic strategies targeting human influenza viruses include vaccines and antivirals. Given variable rates of vaccine efficacy and antiviral resistance, alternative strategies are urgently required to improve disease outcomes. Here we describe the use of HiSeq deep sequencing to analyze host gene expression in primary human alveolar epithelial type II (ATII) cells infected with highly pathogenic avian influenza H5N1 virus. We employed primary human ATII cells isolated from normal human lung tissue donated by patients that underwent lung resection. Human host gene expression following HPAI H5N1 virus (A/Chicken/Vietnam/0008/04) infection of primary ATII cells was analyzed using Illumina HiSeq deep sequencing. Overall design: Human non-tumor lung tissue samples were donated by three anonymous patients undergoing lung resection at Geelong Hospital, Barwon Health, Australia. The research protocols and human ethics were approved by the Human Ethics Committees of Deakin University, Barwon Health and the Commonwealth Scientific and Industrial Research Organisation (CSIRO). An informed consent was obtained from all tissue donors. All research were performed in accordance with the guidelines stated in the National Statement on Ethical Conduct in Human Research (2007). The sampling of normal lung tissue was confirmed by the Victorian Cancer Biobank, Australia.
Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparing Platforms for Messenger RNA Expression Profiling of Archival Formalin-Fixed, Paraffin-Embedded Tissues.
Specimen part, Disease
View SamplesTo study feasibility of gene expression profiling from FFPE tissues using NuGen amplified mRNA hybridized on Affymetrix GeneChip Human Gene 1.0 ST arrays, we designed a pilot study utilizing samples from prostate cancer cohort. We selected samples from large-scale epidemiologic studies and clinical trials representative of a wide variety of fixation times, block ages and block storage conditions.
Comparing Platforms for Messenger RNA Expression Profiling of Archival Formalin-Fixed, Paraffin-Embedded Tissues.
Specimen part
View Samples