Abstract
Tumour angiogenesis is defined by an anarchic vasculature and irregularities in alignment of endothelial cells. These structural abnormalities could explain the variability in distribution of nanomedicines in various tumour models. Then, the main goal of this study was to compare and to characterize the tumour vascular structure in different mouse models of melanoma tumours (B16F10 and SK-Mel-28) and in human melanomas from different patients. Tumours were obtained by subcutaneous injection of 106 B16F10 and 3.106 SK-Mel-28 melanoma cells in C57BL/6 and nude mice, respectively. Tumour growth was evaluated weekly, while vasculature was analysed through fluorescent labelling via CD31 and desmin. Significant differences in tumour growth and mice survival were evidenced between the two melanoma models. A fast evolution of tumours was observed for B16F10 melanoma, reaching a tumour size of 100 mm3 in 7 days compared to SK-Mel-28 which needed 21 days to reach the same volumes. Important differences in vascularization were exposed between the melanoma models, characterized by a significant enhancement of vascular density and a significant lumen size for mice melanoma models compared to human. Immunostaining revealed irregularities in endothelium structure for both melanoma models, but structural differences of vasculature were observed, characterized by a stronger expression of desmin in SK-Mel-28 tumours. While human melanoma mainly develops capillaries, structural irregularities are also observed on the samples of this tumour model. Our study revealed an impact of cell type and tumour progression on the structural vasculature of melanoma, which could impact the distribution of drugs in the tumour environment.
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Acknowledgements
The authors thank the “service commun imagerie et analyse microscopique” and particularly Dr. Mabilleau and Dr. Perrot for their expertise. We are also grateful to Ms. Dumez and Ms. Viau for their technical support.
Funding
The authors thank the “comité départemental du Maine et Loire de la Ligue contre le Cancer” for its financial support for the realization of this project. Furthermore, the authors would like to thank the “Région Pays de la Loire” and the “Erasmus Mundus” program for the financing of the phD program of VP.
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Pautu, V., Mellinger, A., Resnier, P. et al. Melanoma tumour vasculature heterogeneity: from mice models to human. J Cancer Res Clin Oncol 145, 589–597 (2019). https://doi.org/10.1007/s00432-018-2809-z
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DOI: https://doi.org/10.1007/s00432-018-2809-z