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TGFb-induced transcriptome profile in cancer cell lines

ABSTRACT: TGFb plays many roles during tumor progression. It inhibits epithelial cell proliferation in the early stage but promotes tumor invasion by inducing epithelial-to-mesenchymal transition (EMT) in the late stage. Coupled with the strong EMT effect, TGFb exerts an overwhelming influence on modifying the extracellular matrix (ECM), which is generally thought to favor the adhesion and migration of tumor cells [4]. However, the regulation and function of ECM deposited in the tumor microenvironment by TGFb signaling have not been elucidated. Here, we performed a transcriptomic analysis using the human prostate cancer PC3U cell line and the human A549 lung carcinoma cell line. The top-upregulated genes in PC3U cells and A549 cells upon TGFb stimulation were identified to analyze the main regulatory function elicited by TGFb signaling. The GO enrichment analysis showed that extracellular matrix organization and the positive regulation of cell migration were the top regulatory functions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE274287 | GEO | 2024/09/12

REPOSITORIES: GEO

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Project description:Cholangiocarcinoma (CCA) is a hepatobiliary malignancy with dismal prognosis. Currently available models fail to recapitulate the full complexity of CCA, particularly the desmoplastic environment and the interplay between cancer cells and the extracellular matrix (ECM). We aimed to study the role of epithelial tumor cells in ECM deposition and desmoplasia by designing a model encompassing primary epithelial CCA organoids (CCAOs) and native liver and tumor scaffolds obtained by decellularization Background & Aims: Cholangiocarcinoma (CCA) is a hepatobiliary malignancy with dismal prognosis. Currently available models fail to recapitulate the full complexity of CCA, particularly the desmoplastic environment and the interplay between cancer cells and the extracellular matrix (ECM). We aimed to study the role of epithelial tumor cells in ECM deposition and desmoplasia by designing a model encompassing primary epithelial CCA organoids (CCAOs) and native liver and tumor scaffolds obtained by decellularization. Results: Decellularization resulted in effective removal of cells while preserving ECM structure and retaining important characteristics of the tissue origin. When culturing CCAOs in CCA-M, compared to TFL-M and BME, the genome-wide gene expression profile much more resembled the transcriptome of primary CCA tumor tissue in vivo, with an accompanying increase in chemoresistance. CCAOs in decellularized matrix, both CCA-M and TFL-M, exhibited the formation of complex morphological structures, and revealed environment-dependent proliferation and migration dynamics, driven by the occurrence of epithelial-mesenchymal transition (EMT). CCA-M induced specific extracellular matrix protein production in CCAOs, such as fibronectin 1 (FN1), which is related to desmoplasia and patient survival. In TFL-M, lacking the desmoplastic environment, CCAOs were able to initiate a desmoplastic reaction directly through increased production of multiple collagen types. Conclusions: This improved model of cholangiocarcinoma, combining organoids and native extracellular matrix, recapitulates key components of CCA tumor biology, including transcriptome profiles, migration patterns, EMT, and ECM protein production. The increased production of extracellular matrix proteins suggests that epithelial tumor cells can contribute to their own desmoplastic environment.

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TGFb-induced transcriptome profile in cancer cell lines

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