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Clinical & Experimental Metastasis

, Volume 30, Issue 1, pp 83–90 | Cite as

Development of a tridimensional microvascularized human skin substitute to study melanoma biology

  • Laure Gibot
  • Todd Galbraith
  • Jacques Huot
  • François A. Auger
Research Paper

Abstract

Cutaneous malignant melanomas represent an important clinical problem because they are highly invasive, they can metastasize to distant sites and are typically resistant to available therapy. The precise molecular determinants responsible for melanoma progression and chemo-resistance are not yet known, in part due to lack of pertinent experimental models that mimic human melanoma progression. Accordingly, we developed a complex human microvascularized reconstructed skin substitute in which the organized three-dimensional (3D) architecture of the native skin is reproduced. Human melanoma cell lines derived from primary and metastatic sites were added to this 3D model. Our results demonstrate that histological features and behavior of melanoma cells applied in our skin substitute model are specific to their site of origin. In particular, the ability of melanoma cells to cross the dermal–epidermal junction correlates with their metastatic potential. In addition, a potent angiogenic effect was detected for an aggressive metastatic cell line that produces VEGF. The presence of a microvascular network within this model will allow studying a crucial step of the metastatic process. We conclude that such an in vitro human tumor microvascularized reconstructed skin substitute promises to be a versatile and efficient model to investigate skin cancer progression and to screen new anticancer drugs to improve currents clinical treatments.

Keywords

Melanoma Angiogenesis Microvascularization Skin model 3D Model 

Abbreviations

3D

Three-dimensional

BM

Basement membrane

ECM

Extracellular matrix

MRS

Microvascularized reconstructed skin

TMRS

Tumor microvascularized reconstructed skin

Notes

Acknowledgments

We wish to thank Sébastien Larochelle for its technical support concerning melanoma cell lines transduction and Dr Dan Lacroix for his careful reading of this manuscript. This study was supported by the Canadian Institutes of Health Research (Grant SAC-92850).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Laure Gibot
    • 1
  • Todd Galbraith
    • 1
  • Jacques Huot
    • 2
  • François A. Auger
    • 1
    • 3
  1. 1.LOEXCentre de recherche (FRSQ) du CHA de QuébecQuebec CityCanada
  2. 2.Le Centre de recherche en cancérologie de l’Université Laval and CRCHUQQuebec CityCanada
  3. 3.Department of SurgeryFaculty of Medicine, Laval UniversityQuebec CityCanada

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