In vitro 3D models for renal cancer research
Résumé
Von Hippel-Lindau (VHL) syndrome is an autosomal dominant, multi-organ, familial neoplastic syndrome, which is caused by genetic aberrations of the tumor suppressor gene VHL. Germline mutations of the VHL gene predispose affected individuals to the development of angiogenesis and benign and malignant tumors in several organs. The most common VHL-associated tumors are hemangioblastomas and clear cell renal cell carcinoma (RCC) . Anti-angiogenic therapies for kidney cancer have been shown to be promising but they rapidly became ineffective and new therapeutic strategies have to be found. In the last decade 3D models have been developed with the aim of better approaching the natural complex physiology of human tissues.
In this context, we have developed 3D cultures with different stably transfected kidney cell lines. We then tested density and texture of different substrates (matrigel, collagen, matrigel / collagen mix) in order to promote spheroid formation. The shape behavior of the cells in the sphere was recorded by video-microscopy. A migrating image analysis tool was generated to quantify cell movements out of the spheroid. It is thus now possible to use this 3D systems to analyse the biological effects of a wide range of pharmalogical molecules (in collaboration with Cherry Biotech-France)