Spontaneous development of intratumoral heterogeneity in a transposon‐induced mouse model of glioma

• DOI: 10.1111/cas.13579
• Publication Date: 2018-03-25T13:40:35Z
• Authors: Keisuke Sumiyoshi; Hideto Koso; Sumiko Watanabe
• Keywords: Platelet-Derived Growth Factor; Mice, Inbred ICR; 0303 health sciences; Neurofibromin 1; Brain Neoplasms; Original Articles; Glioma; Cell Hypoxia; Disease Models, Animal; Mice; 03 medical and health sciences; DNA Transposable Elements; NIH 3T3 Cells; Animals; Tumor Suppressor Protein p53; Cell Proliferation; Signal Transduction

Glioma is the most common form of malignant brain cancer in adults. The Sleeping Beauty ( SB ) transposon‐based glioma mouse model allows for effective vivo analysis candidate genes. In present study, we developed a transposon vector that encodes triple combination platelet‐derived growth factor subunit A PDGFA ), and sh RNA s against Nf1 Trp53 (shNf1/shp53). Initiation progression were monitored by expression fluorescent protein. Transduction into neural progenitor stem cells NPC subventricular zone SVZ neonatal induced proliferation oligodendrocyte precursor cells, promoted formation highly penetrant gliomas within 2‐4 months. Cells isolated from tumors capable forming secondary tumors. Two vectors, encoding either or shNf1/shp53 co‐electroporated . expressing labeled with unique proteins allowing visualization spatial distribution different genetic alterations same tumor. Tumor located at center expressed higher levels than those periphery, indicating intratumoral heterogeneity spontaneously comprising palisading necrosis strongly , suggesting signaling involved hypoxic responses glioma. vectors are compatible any genetically engineered model, providing useful tool functional genes