[Frontiers in Bioscience, Elite, 9, 162-173, January 1, 2017]

Three dimensional tumor models for cancer studies

Patrice Penfornis 1 , Krishna C. Vallabhaneni 1 , 2 , Amol V. Janorkar 3 , 4 , Radhika R. Pochampally 1 , 5

1Cancer Institute of University of Mississippi Medical Center, Jackson, MS, 2Department of Radiation Oncology of University of Mississippi Medical Center, Jackson, MS, 3Department of Biomedical Materials Science of University of Mississippi Medical Center, Jackson, MS, 4School of Dentistry of University of Mississippi Medical Center, Jackson, MS, 5Department of Biochemistry of University of Mississippi Medical Center, Jackson, MS

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Epithelial tumor structure
4. Mesenchymal tumor structure
5. Tumor spheroid models
    5.1. Suspension culture of stromal and cancer cells
    5.2. Ultra-low cell adherent surfaces
    5.3. The hanging drop technique
    5.4. Microfluidic devices
6. 3D scaffold-based models
7. Future perspectives for 3D culture methods
8. Drug sensitivity patterns
9. Caveats
10. Acknowledgements
11. References

1. ABSTRACT

It is well recognized that one of the major drawbacks of using traditional two dimensional cultures to model the living systems is inaccurately reflecting the physiological manner in which modulators, nutrients, oxygen, and metabolites are applied and removed. Moreover, the two dimensional culture system poorly reflects how different cell types interact with each other in the same microenvironment. Since the first global development of three dimensional (3D) cell culture techniques in the late 1960s, this last decade has seen an explosion of studies to promote 3D models in the fields of regenerative medicine and cancer. The recent surge of interest in 3D cell culture in cancer research is attributable to the interest in developing closer to real life models. The ability to include various cell types and extracellular components reflect more the physiological conditions of tumor microenvironment. In this short review, we will discuss different approaches of 3D culture system models and techniques with a focus on the 3D interactions of cancer cells with stromal cells in the goal to reevaluate old and develop new therapeutics.

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Abbreviations: 3D: three dimensional, 2D: two dimensional, ECM: extracellular matrix, MCTS: multicellular tumor spheroids, MSC: mesenchymal stromal/stem cells, MTT: 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide, PDMS: polydimethylsiloxane, PEG: polyethylene glycol WHO: world health organization

Key Words: Three Dimensional Culture, 3D Cell Culture, Tumor Spheroids, 3D Scaffold, Bioprinting, Microfluidic, Drug Screening, Review.

Send correspondence to: Radhika Pochampally, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216, Tel: 601-815-1979, Fax: 601-815-6806, E-mail: rpochampally@umc.edu