Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Comparison of spheroid-based 3-dimensional culture to monolayer of larynx carcinoma cell line HLaC78.

ABSTRACT: In vitro proliferation and/or invasion tests (such as MTT assay, Boyden Chamber Assay, Scratch assay) using established and well-characterized cell lines can provide easy and reproducible tools to investigate anti-tumour or anti-invasion agents ex vivo. However, in vivo cells in a tissue context interact with neighbouring cells and extracellular matrix components. In 2-dimensional monolayer cultures cells tend to loose tissue-specific properties. 2-D culture models therefore seem unsuitable to mimic the behaviour of cells in a natural, 3-dimensional microenvironment, especially for testing of growth or invasion inhibiting substances. Spheroids on the other hand resemble in many aspects solid, non-vascularized tumour tissue. Within this study the larynx carcinoma cell line HLaC78 was used as a model for comparing overall gene expression in 2D monolayer culture with 72 hrs old HLaC78 multicellular spheroids, providing evidence for extensive restructuring of gene expression in the 3-dimensional context.

ORGANISM(S): Homo sapiens

SUBMITTER: Claus Scholz

PROVIDER: E-GEOD-67495 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Spheroid-based 3-dimensional culture models: Gene expression and functionality in head and neck cancer.

Schmidt Marianne M Scholz Claus-Juergen CJ Polednik Christine C Roller Jeanette J

Oncology reports 20160121 4

In the present study a panel of 12 head and neck cancer (HNSCC) cell lines were tested for spheroid formation. Since the size and morphology of spheroids is dependent on both cell adhesion and proliferation in the 3-dimensional (3D) context, morphology of HNSCC spheroids was related to expression of E-cadherin and the proliferation marker Ki67. In HNSCC cell lines the formation of tight regular spheroids was dependent on distinct E-cadherin expression levels in monolayer cultures, usually result ...[more]

PMID: 26797047

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Project description:Full title: Comprehensive Characterization of Three-Dimensional Models for Prostate Cancer Growth and Invasion in Laminin-rich Extracellular Matrix Prostate Cancer (PrCa) cells undergo acinar morphogenesis and spheroid formation in three-dimensional (3D) culture, supported by laminin-rich extracellular matrix (lrECM, Matrigel). We developed miniaturized 3D model systems that facilitate investigation of morphogenesis and invasion of normal and PrCa cell lines in lrECM. Primary and non-transformed cell lines formed round structures with strong cell-cell contacts and epithelial polarization, lumen and a complete basal lamina (BL). In contrast, most PrCa cell lines formed either defective, “mass” spheroids with incomplete BL, or invasive “stellate” structures. The bioinformatic analyses of genome-wide mRNA expression data revealed massive alteration of key functional and signaling pathways in 3D cultures, with lipid and steroid metabolism, epigenetic reprogramming, and differentiation-related transcription factors induced across all cell lines by lrECM. In invasive cells, AKT, PI3Kinase, mTOR, and hedgehog signaling pathways were most highly activated, validated by small molecule inhibitors compounds specifically targeting key regulatory molecules. Compounds against AKT and PI3kinase pathways were significantly more effective in invasive cells, compared to mass or round/normal phenotype spheroids, and monolayer culture. A severe morphologic conversion was observed in PC-3 and PC-3M cells, transforming initially round, normal-appearing epithelial spheroids into rapidly invading cell masses. Markers for EMT (epithelial-mesenchymal transition) were highly expressed already in early stage, round spheroids prior to invasive conversion, and were not further increased in invasive cells. This indicates that PrCa cells can display extraordinary plasticity. EMT may be involved in providing a metastable genotype that allows morphological transformation, but is not be required for invasive processes themselves. Total RNA was obtained from non-transformed prostate epithelial cells and prostate cancer cells cultured in monolayer and three-dimensional laminin-rich extracellular matrix (growth factor-reduced Matrigel).

Dataset Information

Comparison of spheroid-based 3-dimensional culture to monolayer of larynx carcinoma cell line HLaC78.

Publications

Spheroid-based 3-dimensional culture models: Gene expression and functionality in head and neck cancer.

Similar Datasets

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