Multicellular spheroids: a three‐dimensional<i>in vitro</i>culture system to study tumour biology

Kunz-Schughart, Leoni A.; Kreutz, Marina; Knuechel, Ruth

doi:10.1046/j.1365-2613.1998.00051.x

Cited by 305 publications

(250 citation statements)

References 155 publications

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“…To address this, the versatile multicellular spheroid (MCTS) model (Kunz-Schughart et al, 1998;Santini and Rainaldi, 1999) was chosen to investigate the influence that P-gp exerts on drug distribution in solid tumours. In order to examine drug distribution patterns within tumour spheroids (TS), a confocal fluorescence microscopy technique was employed, a particular advantage being the ability to measure drug distribution in intact tissue.…”

mentioning

confidence: 99%

The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models

et al. 2003

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Solid tumours display a complex drug resistance phenotype that involves inherent and acquired mechanisms. Multicellular resistance is an inherent feature of solid tumours and is known to present significant barriers to drug permeation in tumours. Given this barrier, do acquired resistance mechanisms such as P-glycoprotein (P-gp) contribute significantly to resistance? To address this question, the multicellular tumour spheroid (MCTS) model was used to examine the influence of P-gp on drug distribution in solid tissue. Tumour spheroids (TS) were generated from either drug-sensitive MCF7 WT cells or a drug-resistant, P-gp-expressing derivative MCF7 Adr . Confocal microscopy was used to measure time courses and distribution patterns of three fluorescent compounds; calcein-AM, rhodamine123 and BODIPY-taxol. These compounds were chosen because they are all substrates for P-gp-mediated transport, exhibit high fluorescence and are chemically dissimilar. For example, BODIPY-taxol and rhodamine 123 showed high accumulation and distributed extensively throughout the TS WT , whereas calcein-AM accumulation was restricted to the outermost layers. The presence of P-gp in TS Adr resulted in negligible accumulation, regardless of the compound. Moreover, the inhibition of P-gp by nicardipine restored intracellular accumulation and distribution patterns to levels observed in TS WT . The results demonstrate the effectiveness of P-gp in modulating drug distribution in solid tumour models. However, the penetration of agents throughout the tissue is strongly determined by the physico-chemical properties of the individual compounds.

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confidence: 99%

The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models

et al. 2003

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“…Indeed, 3-D was expected to be the most appropriate model for mimicking in vivo mRNA levels: paraffin sections of spheroids clearly showed that spheroid histoarchitecture was similar to in vivo tumour aggregates of disseminated carcinoma in ascites fluid, thereby suggesting the interest of spheroids as an in vivo-like model (Kunz-Schughart et al, 1998;Santini and Rainaldi, 1999). Interestingly, our results demonstrate that the 3-D spheroid is the most appropriate model for a limited subset of genes in a given tumour.…”

Section: Genetics and Genomicsmentioning

confidence: 57%

Gene expression profiles of bladder cancers: evidence for a striking effect of in vitro cell models on gene patterns

et al. 2002

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In order to assess the effect of in vitro models on the expression of key genes known to be implicated in the development or progression of cancer, we quantified by real-time quantitative PCR the expression of 28 key genes in three bladder cancer tissue specimens and in their derived cell lines, studied either as one-dimensional single cell suspensions, two-dimensional monolayers or three-dimensional spheroids. Global analysis of gene expression profiles showed that in vitro models had a dramatic impact upon gene expression. Remarkably, quantitative differences in gene expression of 2 -63-fold were observed in 24 out of 28 genes among the cell models. In addition, we observed that the in vitro model which most closely mimicked in vivo mRNA phenotype varied with both the gene and the patient. These results provide evidence that mRNA expression databases based on cancer cell lines, which are studied to provide a rationale for selection of therapy on the basis of molecular characteristics of a patient's tumour, must be carefully interpreted.

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“…Considering that multicellular spheroid cultures can closely reproduce some biological features of tumors and improve the relevance of results obtained by in vitro studies [39][40][41], we used three-dimensional MCF7 cultures as an experimental model. MCF7 cell-cell adhesion was enhanced following a 48h exposure to OHT and EGF (Fig.…”

Section: Oht and Egf Induce Mcf7 Cell-cell Adhesion In Three-dimensiomentioning

confidence: 99%

E-cadherin mediates the aggregation of breast cancer cells induced by tamoxifen and epidermal growth factor

Mauro

Pellegrino

Lappano

et al. 2009

Breast Cancer Res Treat

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In the present study, we evaluated the ability of 4-hydroxytamoxifen (OHT) and epidermal growth factor (EGF) to regulate homotypic adhesion in MCF7 breast cancer cells. Our results demonstrate that OHT and EGF activate the E-cadherin promoter, increase E-cadherin mRNA and protein expression and enhance homotypic aggregation of MCF7 cells. Interestingly, an ERα and EGFR cross-talk is involved in the E-cadherin expression by OHT and EGF as demonstrated by knocking-down either receptor. On the basis of our findings, the well-established cross-talk between ERα and EGFR could be extended to the modulation of E-cadherin expression by OHT and EGF. Thus, the potential ability of tamoxifen to induce cell-cell aggregation may contribute to the biological response of pharmacological intervention in breast cancer patients.3

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Multicellular spheroids: a three‐dimensionalin vitroculture system to study tumour biology

Cited by 305 publications

References 155 publications

The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models

The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models

Gene expression profiles of bladder cancers: evidence for a striking effect of in vitro cell models on gene patterns

E-cadherin mediates the aggregation of breast cancer cells induced by tamoxifen and epidermal growth factor

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