Project description:Chronic lymphocytic leukemia shows a variable clinical course which is associated with distinct alterations such as chromosomal aberrations, gene mutations or IGHV mutation status. Refining biologic categories may help to improve clinical management with available and future treatment, lymphoma/leukemia celllines and non-tumour cells of the microenvironment can be used for models to better categorize biologic CLL entities. We used Affymetrix Exon 1.0 ST microarrays to investigate differences in CLL biology.
Project description:The composition and remodelling of the extracellular matrix (ECM) are important factors in the development and progression of cancers, and the ECM is implicated in promoting tumour growth and restricting anti-tumour therapies through multiple mechanisms. The characterisation of differences in ECM composition between normal and diseased tissues may aid in identifying novel diagnostic markers, prognostic indicators and therapeutic targets for drug development. Using tissue from non-small cell lung cancer (NSCLC) patients undergoing curative intent surgery, we characterised quantitative tumour-specific ECM proteome signatures by mass spectrometry, identifying 161 matrisome proteins differentially regulated between tumour tissue and nearby non-malignant lung tissue. We defined a collagen hydroxylation functional protein network that is enriched in the lung tumour microenvironment. We validated two novel putative extracellular markers of NSCLC, the collagen cross-linking enzyme peroxidasin and a disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16), for discrimination of malignant and non-malignant lung tissue. These proteins were up-regulated in lung tumour samples, and high PXDN and ADAMTS16 gene expression was associated with shorter survival of lung adenocarcinoma and squamous cell carcinoma patients, respectively. These data reveal tumour matrisome signatures in human NSCLC.
Project description:Tumour-initiating cells (TICs), also termed as cancer stem cells, contribute to tumour initiation, metastasis, progression and drug resistance. Metabolic reprogramming is a cancer hallmark and plays vital roles in liver tumorigenesis. However, the role of metabolic reprogramming in TICs remains poorly explored.Here we isolated mitochondria from liver TICs and non-TICs, and detected the expression levels of mitochondrial encoded circRNAs in TICs and non-TICs.
Project description:The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains largely elusive. Here we examined the effects of activation of the entire miR-17-92 cluster on global protein expression in neuroblastoma cells. In this dataset we deposit global mRNA expression data obtained form primary neuroblastoma tumour cells. This data was used to demonstrate negative correlation between TGFB target gene expression and expression of the miR-17-92 cluster.
Project description:Active immunotherapy is a promising strategy for anti-angiogenic cancer therapy. Recently, we have reported that a vaccine using human umbilical vein endothelial cells (HUVECs) induced specific anti-endothelial immune responses in the most of immunized patients, and resulted in tumor regression in some patients with recurrent malignant brain tumors, whereas not in colorectal cancer patients. In this study, we hypothesized that non-hypoxic perivascular tumor associated macrophages (TAMs) in colorectal cancer, but not in glioblastoma, might negatively alter the therapeutic efficacy of anti-angiogenic active immunotherapy. To test this hypothesis, we examined global gene expression profiles of non-hypoxic macrophages stimulated in vitro by soluble factors released from tumor cells of human glioblastoma U-87MG (‘brain TAMs’) or colorectal adenocarcinoma HT-29 (‘colon TAMs’). Murine non-hypoxic TAMs were induced in vitro by incubation with soluble factors released from human cancer cell lines U-87MG ('brain TAMs') or HT-29 ('colon TAMs'), for RNA extraction and subsequent hybridization on Affymetrix microarrays. To evaluate homogeneous macrophage populations at different tumour developmental stages, RNA aliquots of control macrophages and TAMs obtained at five different time-points, i.e. 8h, 16h, 24h, 32h and 40h, were pooled and used for screening of differentially expressed genes. The experiments for TAMs as well as for control unstimulated macrophages were performed in triplicates.
Project description:Agrobacterium tumefaciens, a bacterial species found in temperate soils world wide, is the causative agent of crown gall disease on many plants. A. tumefaciens-induced tumours are feared in orchards and vineyards because of their pathological interference with nutrient and water supply which results in crop decline. Small wounds at the crown of the plant, usually induced by wind-bending, are potential entry sites for the bacterium. The tumorous growth is initiated by the integration and expression of the T-DNA of the bacterial Ti plasmid within the plant nuclear DNA. The T-DNA encodes enzymes catalysing the synthesis of increased concentrations of auxin and cytokinin, and of opines which stimulate cell division and enlargement. The fast growing tumours have been shown to be a strong nutrient sink on their host plants. As a matter of fact, sugar and K+ content were found to be up to 10- and 5-fold, respectively, higher in this tissue and transpiration was about 15 times increased compared to normal tissue. Whereas the morphological structure as well as some physiological and biochemical parameters of the tumour have been analysed in detail, little is known about the underlying gene expression pattern. Proliferation and growth of the tumour induced by Agrobacterium tumefaciens is obviously due to the extraordinary high concentration of phytohormons, minerals and metabolites. Their influence on regulation of gene transcription will provide information on the mechanisms underlying fast tumour growth. In a project funded by the DFG we recently started to investigate the role of solute transporter for tumour development on the model plant Arabidopsis thaliana. By comparing the expression pattern of RNA preparations from Arabidopsis tumour and non-tumour tissue, we will be able to identify genes which facilitate crown gall development. For the expression analysis with an Affymetrix full genome chip we will induce tumours at the base of an injured Arabidopsis inflorescence stalk (var. Wassilewskija, WS-2). RNA will be extraxted from tumour and injured non-tumor inflorescence stalk tissue using the RNeasy Plant Mini Kit (Qiagen), followed by a DNase treatment to eliminate DNA contamination.