Neoplastic transformation and angiogenesis in the thymus of transgenic mice expressing SV40 T and t antigen under an L-pyruvate kinase promoter (SV12 mice).

Using several techniques, we have assessed morphological characteristics of a malignant thymic tumour in SV12 transgenic (Tg) mice expressing SV40 T and t antigens under control of an L-PK promoter. We describe the development of a carcinoma originating from thymic hyperplasia and followed by the formation of a benign tumour composed chiefly of medullary epithelial cells expressing the transgene and of lymphocytes, a pathology very rarely reported in mice. Our study of the SV12 Tg mice represents the first description of a model of a pure malignant thymic tumour associated with extensive angiogenesis maintained in numerous descendants. The formation of a large tumoral neovascular network, observed here, has never been described in human and/or experimental thymic tumours. Tumoral transformation and angiogenesis are demonstrated by immunolabelling with antibodies against various cytokeratins (CKs) of different molecular weights, vascular endothelial cell markers and VEGF/receptor-2 (Flk-1) present on the neovascular endothelial cells. Different points raised by the originality of this model are discussed. These include the medullary nature of the cells expressing the SV40 transgene and their relationship with the tumoral development. The subset of different molecular weight CK components and their modifications are also considered, as well as the presence of type IV epithelial cells, progenitors of medullary epithelial cells. Finally, the cell signals involved in angiogenesis and the possible action of an angiogenic factor, probably secreted by the tumoral cells themselves, are discussed.