[Animal Modeling ]- A Transgenic Animal Model for Tumor Angiogenesis

  There are many reports on transgenic animal models related to tumor angiogenesis. There are currently three types of transgenic mouse models used for tumor angiogenesis:

  1. The RIP-Tag transgenic mouse model is induced by the oncogene SV40Tag and controlled by the insulin gene regulatory region, which is a pancreatic islet β Cellular tumors. Oncogene expression can be observed at 8-21 days of embryonic stage, followed by scattered proliferation of pancreatic islets, of which 50% become highly proliferative islets, possessing the characteristics of tumor cells in histological morphology and proliferation rate. Among them, 20% have obvious angiogenesis, and 10% can become solid tumors. Histological testing of new blood vessels has confirmed that: ① The pre cancerous lesions in the RIP Tag transgenic mouse model are very obvious in all stages, and there is a angiogenesis phase after the proliferation phase. ② New blood vessels grow well before the tumor cells undergo widespread malignant transformation.

  The BPV1.69 transgenic mouse model is induced by the genome of the papillomavirus and is a dermal fibrosarcoma. The tumor formation in this model can be divided into three stages: normal, mild skin fibroma formation, and invasive skin fibroma formation. The three stages are accompanied by the expression of c-jun, jun-B oncogenes, and their related transcription factors AP-1. According to vWF (Von Willebrand) immunostaining, microvascular density significantly increases during the formation stage of invasive skin fibroma. The results indicate that there is activation of blood vessels before the formation of skin fibrosarcoma. The experiment of in vitro cell lines also showed that in each stage of the gradual formation of skin fibrosarcoma, there were corresponding independent vascular initiation stages. The conditioned medium for normal skin cells and mild skin fibrosarcoma cells did not have proendothelial cell division and proliferation activity, while the conditioned medium for invasive skin fibrosarcoma cells and skin fibrosarcoma cells had proendothelial cell division and proliferation activity.

  The K14-HPV16 transgenic mouse model is derived from basal keratinocytes and mainly expresses the human papillomavirus type 16 oncogene, controlled by the keratin 14 gene regulatory region. It is an epidermal squamous cell carcinoma. This model is accompanied by activation of angiogenesis initiation at all stages of tumor formation. At the age of one month, K14-HPV16 transgenic mice showed a slight increase in capillary density in the dermis, while in the early and advanced stages of dysplasia, both the number and distribution density of capillaries were significantly increased. This phenomenon indicates that the formation of low-grade damaged blood vessels starts in the early stage, moving from a stationary state to a moderate degree of neovascularization, while the formation of blood vessels increases significantly in the stage of high proliferation and tumor infiltration.