Second, GSEA and pathway analysis only provide induced change as a whole, thus individual interactions cannot be evaluated. First, since expression profiles of cancer cells and stromal cells are treated independently, interactions between them cannot be explicitly evaluated. These approaches are effective in identifying gene sets or pathways contributing to the change. xenograft vs in cell line, or before vs after the addition of a molecule which would change the cancer-microenvironment, and subsequently apply Gene Set Enrichment Analysis (GSEA) or pathway analysis. Like conventional single-species gene expression analysis, all of these methods compare gene expression profiles in two conditions, e.g. Several computational methods have been developed to analyze microarrays or RNA-Seq data from cancer xenograft mouse models. Given that there is approximately 15 % sequence difference between human and mouse exon sequences, simultaneous transcriptome analysis of cancer and stroma can be achieved using RNA-Seq or species-specific microarray. Xenograft cancers establish microenvironment by inducing mouse-derived stromal cells such as fibroblast and vascular cells, and can closely resemble the original cancer growing in a patient. Xenograft cancers from human-derived cells grown in immune-compromised mice have been extensively used to study cancer and its microenvironment.
WIFI DONGLE YANG SUPPORT TANAKA NEW SAKURA 22 DRIVER
However, compared to targeting driver ‘mutations’ which are tractable by genome-wide comparison of mutation frequency, exploration of driver ‘interactions’ is far more challenging due to the exponential number of possible interactions between proteins and lack of high-throughput methods that can quantitatively interpret the cancer-stromal interactions. For example, inhibition of Hedgehog signaling improves delivery and efficacy of gemcitabine in a mouse pancreatic cancer model.
Inhibition of cancer stromal interaction may prevent neovascularization, invasion, and metastasis and improve anti-cancer drug delivery. Recently, there has been a growing interest in targeting cancer microenvironment for cancer treatment. Thus cancer microenvironment is regarded as a key contributor for epithelial-mesenchymal transition of the cancer cells, angiogenesis, cancer progression and metastasis, and development of drug resistance.
Conversely, cancer cells promote fibroblast proliferations, immune cell migration and angiogenesis through signal transduction. Stromal cells in cancer microenvironment promote maintenance, growth and progression of cancer cells through the release of humoral factors and direct cell contact. Cancer cells generally survive in microenvironment surrounded by non-cancer “stromal” cells such as endothelial cells, fibroblasts and immune cells.
0 kommentar(er)
