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Gene expression profile of two colorectal cancer HT29 and DLD-1 cell lines cultivated in 2-dimensional or 3-dimensional cell culture enriched with laminin rich extracellular matrix proteins

ABSTRACT: Conventional monolayer cell cultures used in cancer research accumulated basic knowledge of carcinogenesis which correlates with basic observations in tumor biology. Nevertheless, attempts to transfer accumulated cancer biology knowledge to clinical applications fails in most of the cases. Gathered data suggest that 2D cell culture models lack many features of tumor tissue in vivo. Although it has been demonstrated that cancer cells are generally more resistant to various types of treatments when cultured in extracellular matrix (ECM) based 3D cultures it is not clear if this phenomenon is attributed to the ECM dependent gain of function or the loss of non-physiological cellular state demonstrated while cultured at 2D conditions. To address the question of which universal molecular mechanisms if any are gained/lost in ECM-dependent manner we carried out genome wide gene expression analysis of human colorectal carcinoma DLD-1 and HT-29 cell lines cultured in 2D or ECM based 3D conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE75551 | GEO | 2015/12/01

SECONDARY ACCESSION(S): PRJNA304520

REPOSITORIES: GEO

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Gene expression profile of mouse Lewis lung carcinoma cell line cultivated in 2-dimensional or 3-dimensional cell culture enriched with laminin rich extracellular matrix proteins.

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2015-12-10 | E-GEOD-75863 | biostudies-arrayexpress

Gene expression profile of mouse Lewis lung carcinoma cell line cultivated in 2-dimensional or 3-dimensional cell culture enriched with laminin rich extracellular matrix proteins.

2015-12-10 | GSE75863 | GEO

Gene expression profile of two colorectal cancer HT29 and DLD-1 cell lines treated with single or fractionated ionizing radiation doses under 3D cell culture conditions.

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2015-12-12 | E-GEOD-75915 | biostudies-arrayexpress

Gene expression profile of two colorectal cancer HT29 and DLD-1 cell lines treated with single or fractionated ionizing radiation doses under 3D cell culture conditions.

2015-12-12 | GSE75915 | GEO

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2013-06-03 | E-GEOD-28381 | biostudies-arrayexpress

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2017-11-30 | GSE102722 | GEO

Three-dimensional tumor cell growth stimulates autophagic flux and recapitulates chemotherapy resistance

Project description:Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and human tumors in preclinical drug testing. Besides 3D growth, it is also advantageous to simulate shear stress, compound flux and removal of metabolites, e.g. via bioreactor systems, through which culture medium is constantly pumped at a flow rate reflecting physiological conditions. Here, we show that both Staticic 3D growth and 3D growth within a bioreactor system modulate key hallmarks of cancer cells, including proliferation and cell death as well as macroautophagy, a recycling pathway often activated by highly proliferative tumors to cope with metabolic stress. The autophagy-related gene expression profiles of 2D- and 3D-grown cells are substantially different, with the 3D-grown cells exhibiting an expression profile closely resembling the (patho-) physiological Statice of a tumor. Underscoring the importance of this pathway, autophagy-controlling transcription factors, such as TFEB and FOXO3, are upregulated in tumors, and 3D-grown cells have increased expression compared with cells grown in 2D conditions. Three-dimensional cultures depleted of the autophagy mediators BECN1, ATG5 or ATG7 or the transcription factor FOXO3, are more sensitive to cytotoxic treatment. Accordingly, combining cytotoxic treatment with compounds affecting late autophagic flux, such as chloroquine, renders the 3D-grown cells more susceptible to therapy and increases intracellular doxorubicin concentration to the level of 2D-grown cells. Altogether, 3D cultures are a valuable tool to study drug response of tumor cells, as these models recapitulate (patho-) physiologically relevant pathways, such as autophagy.

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3D Culture of human lung fibroblasts decreases proliferative and increases extracellular matrix remodeling genes

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