Cancer Letters

Cancer Letters

Volume 396, 28 June 2017, Pages 10-20
Cancer Letters

Original Article
A 3D model of tumour angiogenic microenvironment to monitor hypoxia effects on cell interactions and cancer stem cell selection

https://doi.org/10.1016/j.canlet.2017.03.006Get rights and content
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Highlights

  • 3D spheroids tumour model of relevant angiogenic/hypoxic microenvironment.

  • Cancer stem like cell (CSCs) phenotype is hypoxia-stabilized.

  • CSCs recruit selectively early endothelial progenitor cells (EEPCs) in hypoxia.

  • Dysregulation of tumour microRNAs in 3D model of tumour microenvironment.

Abstract

Tumour microenvironment determines the fate of treatments. Reconstitution of tumour conditions is mandatory for alternative in vitro methods devoted to cancer development and the selection of therapeutic strategies. This work describes a 3D model of melanoma growth in its environment. Introducing means to mimic tumour angiogenesis, which turns on tumour progression, the model shows that melanoma tumour spheroids allow reconstitution of solid tumours with stromal cells. Angiogenesis evidenced the differential recruitment of endothelial cells (EC) from early progenitors (EEPCs) to mature ECs. Hypoxia was the key parameter that selected and stabilized melanoma cancer stem like cells (CSCs) phenotype based on aldehyde dehydrogenase expression as the best criterion. The 3D-tumour-model demonstrated the distinct reactivity of ECs toward tumour cells in terms of cellular cross-talk and humoral response. Intra-spheroid cell-to-cell membrane dye exchanges, mediated by intercellular interactions, uncovered the melanoma-to-EEPC cooperation. The resulting changes in tumour milieu were evidenced by the chemokinic composition and hypoxia-related variations in microRNA expression assessed in each cellular component of the spheroids. This method brings new tools to decipher the molecular mechanism of tumour-mediated cell recruitment and for in vitro assessment of therapeutic approaches.

Keywords

Angiogenesis
Endothelial progenitors
Hypoxia
microRNA
Recruitment
Spheroid tumour model

Cited by (0)

1

Department of Clinical Immunology, Institute of Paediatrics, Faculty of Medicine, Jagiellonian, University Medical College, ul. Wielicka 265, 30-663, Krakow, Poland.

2

Department of Mineral and Analytical Chemistry, University of Geneva, CH-1211, Geneva 4.