Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA163113 | ENA |
REPOSITORIES: ENA
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Project description:Interactions of cancer cells with the vasculature are essential for tumor growth and likely promote metastatic progression. Endothelial cell content and lympho-vascular invasion are generally associated with tumor aggressiveness, however, these features are generally not employed in the clinic. We aimed to determine if endothelial cell gene expression signatures could be utilized to better characterize breast tumor biology, and to establish if vascular cell-derived signatures could provide information to predict tumors likely to metastasize. Here we report on the identification of a gene signature for vascular endothelial cells, and a second for cancer-activated vasculature. Both signatures independently identify subsets of aggressive breast cancers. Interestingly, the vascular content signature and a previously identified hypoxia signature both provide prognostic information beyond currently utilized clinical parameters and intrinsic subtype classifications. In these studies, we also examined the relationship that the breast cancer subtypes have with vascular gene expression profiles, and found that claudin-low tumors and cell lines express vascular gene expression profiles and displayed endothelial-like tube formation when grown in three-dimensions. These findings are directly applicable to clinical care and therapeutic treatment design as they identify highly aggressive subsets of tumors with genetic and morphologic vascular properties. reference x sample
2014-01-01 | E-GEOD-37145 | biostudies-arrayexpress
Project description:Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes
| PRJNA246530 | ENA
Project description:Interactions of cancer cells with the vasculature are essential for tumor growth and likely promote metastatic progression. Endothelial cell content and lympho-vascular invasion are generally associated with tumor aggressiveness, however, these features are generally not employed in the clinic. We aimed to determine if endothelial cell gene expression signatures could be utilized to better characterize breast tumor biology, and to establish if vascular cell-derived signatures could provide information to predict tumors likely to metastasize. Here we report on the identification of a gene signature for vascular endothelial cells, and a second for cancer-activated vasculature. Both signatures independently identify subsets of aggressive breast cancers. Interestingly, the vascular content signature and a previously identified hypoxia signature both provide prognostic information beyond currently utilized clinical parameters and intrinsic subtype classifications. In these studies, we also examined the relationship that the breast cancer subtypes have with vascular gene expression profiles, and found that claudin-low tumors and cell lines express vascular gene expression profiles and displayed endothelial-like tube formation when grown in three-dimensions. These findings are directly applicable to clinical care and therapeutic treatment design as they identify highly aggressive subsets of tumors with genetic and morphologic vascular properties.
2014-01-01 | GSE37145 | GEO
Project description:The primary goal of this study is to identify molecular subtypes of breast cancer through gene expression profiles of 327 breast cancer samples and determine molecular and clinical characteristics of different breast cancer subtypes. We studied expression signatures of different cellular functions (e.g., cell proliferation/cell cycle, wound response, tumor stromal response, vascular endothelial normalization, drug esponse genes, etc.) in different breast cancer molecular subtypes and investigated how microarray-based breast cancer molecular subtypes may be used to guide treatment. Gene expression profiles of 327 breast cancer samples were determined using total RNA and Affymetrix U133 plus 2.0 arrays.
2011-04-24 | E-GEOD-20685 | biostudies-arrayexpress
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:Epithelial ovarian cancer is morphologically and clinically heterogeneous. Transcriptional profiling has revealed molecular subtypes (referred to as M-bM-^@M-^\C-signaturesM-bM-^@M-^]) that correlate to biological as well as clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and to investigate similarities to the intrinsic molecular subtypes of breast cancer. Global gene expression profiling was performed using Illumina's HT12 Bead Arrays and applied to 59 fresh-frozen ovarian tumors. SAM analysis revealed enrichment of cell cycel processes among the malignant tumors, in line with malignant tumors being highly proliferative. The borderline tumors were split between the malignant and benign tumor clusters, indicating that borderline tumors have both malignant and benign features. Furthermore, nearest centroid classification was performed applying previously published gene profiles for the ovarian cancer C-signatures and the intrinsic breast cancer subtypes, respectively, and showed significant correlations between the malignant serous tumors and the highly aggressive C1, C2 and C4 ovarian cancer signatures, and the basal-like breast cancer subtype. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer C3 signature. The borderline tumors, on the other hand, correlated significantly to the Luminal A breast cancer subtype. These findings remained when analyzed in a large, independent dataset. The data in this study link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, including an aggressive phenotype, frequent TP53 mutations and a high degree of genomic instability, and suggest that biomarkers and targeted therapies may overlap between these subsets of ovarian and breast cancers. Finally, the link between benign and borderline ovarian cancer and luminal breast cancer may indicate endocrine responsiveness in a subset of ovarian cancers. Total RNA obtained from serous ovarian adenocarcinomas, adenomas and borderline tumors. Gene expression profiling using Illumina's HT12 v4 bead arrays. Application of ovarian cancer molecular subtypes and intrinsic breast cancer subtypes using nearest centroid classification. KRAS and BRAF mutation analyses in the malignant and borderline tumors.
2014-08-15 | E-GEOD-57477 | biostudies-arrayexpress
Project description:DNA methylation epigenotypes in Breast Cancer Molecular Subtypes
| PRJNA127571 | ENA
Project description:Cancer development and progression depend on tumor cell intrinsic factors, the tumor microenvironment and host characteristics. Despite the identification of the plasticity of adipocytes, the primary breast stromal cells, both in physiology and cancer, we lack a complete understanding of mechanisms that regulate adipocyte-tumor cell crosstalk. Here we dissected the breast cancer crosstalk with adipocytes and studied relevant molecules. We identified that the ability of breast cancer cells to dedifferentiate adipocytes is intrinsic subtype-dependent, with all breast cancer subtypes, except for HER2+ER+ subtype, capable of inducing this phenomenon. Crosstalk between breast cancer cells and adipocytes in vitro increased cancer stem-like features and recruitment of pro-tumorigenic immune cells, through chemokine production. Serum amyloid A1 (SAA1) was in vitro identified as a regulator of the adipocyte dedifferentiation program in triple-negative breast cancer (TNBC) through CD36 and P2XR7 signaling. In human TNBCs, SAA1 expression was associated with CAA infiltration, inflammation, stimulated lipolysis, stem-like properties and distinct tumor immune microenvironment. Our findings provide evidence that interaction between tumor cells and adipocytes through SAA1 release is relevant to the aggressiveness of TNBC, potentially supporting its targeting.
2024-01-15 | PXD041186 | Pride