Pulmonary alveoli are complex architectural units thought to undergo endogenous or pharmacologically induced programs of regeneration and degeneration. To study the molecular mechanism of alveoli loss mice were calorie restricted at different timepoints. Lungs were harvested and processed for RNA extraction.
Calorie-related rapid onset of alveolar loss, regeneration, and changes in mouse lung gene expression.
Time
View SamplesIt has been shown that dexamethasone (Dex) impairs the normal lung septation that occurs in the early postnatal period. Treatment with retinoic acid (ATRA) abrogates the effects of Dex. To understand the molecular basis for the Dex indiced inhibition of the formation of the alveoli and the ability of ATRA to prevent the inhibition of septation, gene expression was analyzed in 4-day old mice treated with diluent (control), Dex-treated and ATRA+Dex-treated.
DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation.
No sample metadata fields
View SamplesIdentification of genes that are involved in self-seeding by comparing gene expression profiles between parental MDA-MB-231 cells and seeder cells (MDA-231-S1a and S1b)
Tumor self-seeding by circulating cancer cells.
No sample metadata fields
View SamplesComparisons among breast cancer metastases at different organs revealed distinct microenvironments as characterized by cytokine content.
Latent bone metastasis in breast cancer tied to Src-dependent survival signals.
No sample metadata fields
View SamplesComparisons among breast cancer metastases at different organs revealed distinct microenvironments as characterized by cytokine content.
Latent bone metastasis in breast cancer tied to Src-dependent survival signals.
No sample metadata fields
View SamplesComparisons among breast cancer metastases at different organs revealed distinct microenvironments as characterized by cytokine content.
Latent bone metastasis in breast cancer tied to Src-dependent survival signals.
No sample metadata fields
View SamplesMetastasis-initiating cells dynamically adapt to the distinct microenvironments of different organs, but these early adaptations are poorly understood due to the limited sensitivity of in situ transcriptomics. We developed fluorouracil-labeled RNA sequencing (Flura-seq) for in situ analysis with unprecedented sensitivity. Flura-seq utilizes cytosine deaminase (CD) to convert fluorocytosine to fluorouracil, covalently labeling nascent RNA for purification and sequencing. Flura-seq revealed that breast cancer micrometastases in lung and brain exhibit unique, reversible gene signatures depending on the microenvironment. Specifically, the mitochondrial electron transport Complex I and the NRF2-driven antioxidant programs were induced in oxygen-rich pulmonary micrometastases, compared to mammary tumors or brain micrometastases. Loss of Complex I activity, and antioxidant supplementation potentiated pulmonary metastatic growth. We confirm lung metastasis-specific NRF2 overexpression in clinical samples, thus validating Flura-seq's utility in identifying clinically actionable microenvironmental adaptations in early metastasis. The sensitivity, robustness and economy of Flura-seq are broadly applicable beyond cancer research. Overall design: Examination of 5-FU labeled RNAs in cancer cells present in different organs
Flura-seq identifies organ-specific metabolic adaptations during early metastatic colonization.
Cell line, Subject
View SamplesIdentify Wnt3A responsive signature in lung adenocarcinoma cells
WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis.
No sample metadata fields
View SamplesCancer-specific changes in DNA methylation can alter genetic stability, genomic structure, and gene expression. Promoter CpG island methylation can result in transcriptional silencing and plays an important role in the oncogenic process. We used genome-wide analysis to characterize the methylomes of breast cancers with diverse metastatic behavior. Here, we describe the identification of novel groups of breast tumors characterized by the presence or absence of coordinate hypermethylation at a large number of genes, demonstrating the existence of a breast-CpG island methylator phenotype (B-CIMP). B-CIMP imparts a distinct epigenomic profile and is a strong determinant of metastatic potential.
Breast cancer methylomes establish an epigenomic foundation for metastasis.
Specimen part
View SamplesHow organ-specific metastatic traits accumulate in primary tumors remains unknown. We identified a role of the primary tumor stroma in selecting breast cancer cells that are primed for metastasis in the bone. A fibroblast-rich stroma in breast tumors creates a microenvironment that is similar to that of bone metastases in its abundance of the cytokines CXCL12 and IGF1. Heterogeneous breast cancer cell populations growing in such mesenchymal environment evolve towards a preponderance of clones that thrive on CXCL12 and IGF1. Fibroblast-driven selection of bone metastatic clones in mammary tumors is suppressed by CXCL12 and IGF1 receptor inhibition. Thus, a fibroblast-rich stroma in breast tumors can pre-select bone metastatic seeds, promoting the evolution of metastatic traits and the interplay between a primary tumor and its distant metastases.
Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma.
Specimen part
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