ABSTRACT: To confirm that the biology of engineered liver and lung metastases are similar to in vivo metastases, we compared the global gene expression profiles of the engineered liver and lung metastases of HT-29 cells to that of standard tissue culture (plastic), Matrigel culture and in vivo liver metastasis (splenic injection).
Project description:Lymphangioleiomyomatosis (LAM) is a rare disease involving cystic lung destruction by invasive LAM cells. These cells harbor loss-of-function mutations in TSC2, conferring hyperactive mTORC1 signaling. Here, tissue engineering tools are employed to model LAM and identify new therapeutic candidates. Biomimetic hydrogel culture of LAM cells is found to recapitulate the molecular and phenotypic characteristics of human disease more faithfully than culture on plastic. A 3D drug screen is conducted, identifying histone deacetylase (HDAC) inhibitors as anti-invasive agents that are also selectively cytotoxic toward TSC2−/− cells. The anti-invasive effects of HDAC inhibitors are independent of genotype, while selective cell death is mTORC1-dependent and mediated by apoptosis. Genotype-selective cytotoxicity is seen exclusively in hydrogel culture due to potentiated differential mTORC1 signaling, a feature that is abrogated in cell culture on plastic. Importantly, HDAC inhibitors block invasion and selectively eradicate LAM cells in vivo in zebrafish xenografts. These findings demonstrate that tissue-engineered disease modeling exposes a physiologically relevant therapeutic vulnerability that would be otherwise missed by conventional culture on plastic. This work substantiates HDAC inhibitors as possible therapeutic candidates for the treatment of patients with LAM and requires further study.
Project description:We performed an expression profiling study of 168 primary breast tumors, lymph node metastases, and autopsy samples of primary breast tumours and metastases to liver, chest wall, lymph node, lung, and spleen, as well as positive and negative RNA controls, with technical replicates, to assess quality control methodology and probe-level reproducibility of the Illumina DASL microarray assay. The experiment included both Illumina DASL HumanRef-v3 and DASL HT-12; this series includes only the 120 HumanRef-v3 samples . This series includes 120 samples in total: 19 autopsy tissues of the chest wall, liver, lymph nodes, lung, spleen, liver, and breast, 5 negative controls, 6 positive controls, and 90 lymph node metastases.
Project description:Comparison of gene expression data between cell lines grown on 2D tissue culture plastic or 3D matrigel A427, A549, H23, H358, H460, H661, H1437, and H1703 cells were compared
Project description:We performed an expression profiling study of 168 primary breast tumors, lymph node metastases, and autopsy samples of primary breast tumours and metastases to liver, chest wall, lymph node, lung, and spleen, as well as positive and negative RNA controls, with technical replicates, to assess quality control methodology and probe-level reproducibility of the Illumina DASL microarray assay. The experiment included both Illumina DASL HumanRef-v3 and DASL HT-12; this series includes only the 120 HumanRef-v3 samples .
Project description:We performed an expression profiling study of 168 primary breast tumors, lymph node metastases, and autopsy samples of primary breast tumours and metastases to liver, chest wall, lymph node, lung, and spleen, as well as positive and negative RNA controls, with technical replicates, to assess quality control methodology and probe-level reproducibility of the Illumina DASL microarray assay. The experiment included both Illumina DASL HumanRef-v3 and DASL HT-12; this series includes only the 48 HT12 samples .
Project description:RNA-seq data characterising neuroendocrine (NE) and non-NE cells, cultured on plastic or Matrigel, extracted from small cell lung cancer circulating tumour cell derived explants.
Project description:We performed an expression profiling study of 168 primary breast tumors, lymph node metastases, and autopsy samples of primary breast tumours and metastases to liver, chest wall, lymph node, lung, and spleen, as well as positive and negative RNA controls, with technical replicates, to assess quality control methodology and probe-level reproducibility of the Illumina DASL microarray assay. The experiment included both Illumina DASL HumanRef-v3 and DASL HT-12; this series includes only the 48 HT12 samples . This series includes 48 samples in total: 9 positive controls, 4 negative controls, and 35 primary breast tumors and metastatic lymph nodes.
Project description:Gene expression profiling of ErbB2-engineered MCF10A and WT cells in 2D and 3D culture Gene expression profiling of ErbB2-engineered MCF10A and WT cells, 2D and 3D culture, 5 or 6 replicates
Project description:Intratumoral heterogeneity is a driver of breast cancer progression, but the nature of the clonal interactive network involved in this process remains unclear. Here, we optimized the use of optical barcoding to visualize and characterize 31 cancer subclones in vivo. By mapping the clonal composition of thousands of metastases in two clinically relevant sites, the lungs and liver, we found that metastases were highly polyclonal in lungs but not in the liver. Furthermore, the transcriptome of the subclones varied according to their metastatic niche. We also identified a reversible niche-driven signature that was conserved in lung and liver metastases collected during patient autopsies. Among this signature, we found that the tumor necrosis factor–α pathway was up-regulated in lung compared to liver metastases, and inhibition of this pathway affected metastasis diversity. These results highlight that the cellular and molecular heterogeneity observed in metastases is largely dictated by the tumor microenvironment.
Project description:The goal of this study was to compare RNA expression of the A) CEA gene obtained from i) colon intestine organoids cultured in conventional plastic-adherent Matrigel drop overlaid with growth medium; ii) Colon Intestine-Chips derived from organoids in the presence of constant flow and stretch; iii) human colon intestine tissue and to verify whether Colon Intestine-Chip faithfully recapitulates human duodenum tissue and to better understand how much it differs from the organoids from which it’s derived, and B) FLOR1 gene obtained from i) human alveolar epithelial cells in T-25 Flasks, ii) human Alveolus Lung-Chip on day 5 and day 10 of the culture.