RCAS/SCL-TVA Animal Model Allows Targeted Delivery of Polyoma Middle T Oncogene to Vascular Endothelial Progenitors <i>In vivo</i> and Results in Hemangioma Development

Sausville, Justin; Molinolo, Alfredo A.; Cheng, Xiangfei; Frampton, Jon; Takebe, Naoko; Gutkind, J. Silvio; Feldman, Ricardo A.

doi:10.1158/1078-0432.ccr-07-5152

Cited by 9 publications

(4 citation statements)

References 45 publications

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“…Polyoma middle T (PYMT) as an oncogene transforms endothelial cells and hematopoietic stem cells, which exhibit activation of the PI3K1 AKT and mTOR pathways, suggesting a mechanism used by PYMT to transform endothelial progenitors (16). Mutations in CCMI, CCM2, or CCM3 lead to cerebral cavernous malformations, of which CCM3 supports AKT-mediated endothelial cell quiescence and survival, showing the importance of CCM3/ AKT pathway in neural/vascular interactions within the neurovascular unit (17,18).…”

Section: Discussionmentioning

confidence: 99%

Combined Blockade and Akt/Mtor Pathway Inhibits Growth of Human Hemangioma via Downregulation of Proliferating Cell Nuclear Antigen

et al. 2012

Int J Immunopathol Pharmacol

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Protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in the tumorigenesis and progression of multiple tumors, and has been shown to be important therapeutic targets for cancer. The present study aimed to explore the role and molecular mechanisms of AKT/mTOR pathway in human hemangioma (HA). Twenty-five cases of human HA tissues were collected. The expression of AKT, mTOR and proliferating cell nuclear antigen (PCNA) proteins was evaluated using semi-quantitative immunohistochemistry in biopsy samples in different phases of HA. AKT/mTOR pathway was blocked by recombinant small hairpin RNA adenovirus vector rAd5-AKT+mTOR (rAd5-Am), used for infecting proliferating phase HA-derived endothelial cells (HDEC). The expression of AKT, mTOR and PCNA was detected by Real-time PCR and Western blot assays. Cell proliferative activities were determined by MTT assay, and cell cycle distribution and apoptosis were analyzed by flow cytometry. As a consequence, the expression of AKT, mTOR and PCNA was significantly increased in proliferative phase HA, while that was decreased in involutive phase. Combined blockade of AKT/mTOR pathway by rAd5-Am diminished cell proliferative activities, and induced cell apoptosis and cycle arrest with the decreased expression of AKT, mTOR and PCNA in proliferative phase HDEC. In conclusion, the activity of AKT/mTOR pathway was increased in proliferative phase HA, while it was decreased in involutive phase. Combined blockade of AKT/mTOR pathway might suppress cell proliferation via down-regulation of PCNA expression, and induce apoptosis and cycle arrest in proliferative phase HDEC, suggesting thatAKT/mTOR pathway might represent the important therapeutic targets for human HA.

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Section: Discussionmentioning

confidence: 99%

Combined Blockade and Akt/Mtor Pathway Inhibits Growth of Human Hemangioma via Downregulation of Proliferating Cell Nuclear Antigen

et al. 2012

Int J Immunopathol Pharmacol

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“…The approach has now been applied to lentivirus constructs to allow efficient infection of nondividing cells (270). When applied to targeting progenitor cells, MT was able to cause hemangiomas (250).…”

Section: Introduction Of Mt As Dna or Using Viral Vectorsmentioning

confidence: 99%

Lessons in Signaling and Tumorigenesis from Polyomavirus Middle T Antigen

Fluck

Schaffhausen

2009

Microbiol Mol Biol Rev

144

156

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SUMMARY The small DNA tumor viruses have provided a very long-lived source of insights into many aspects of the life cycle of eukaryotic cells. In recent years, the emphasis has been on cancer-related signaling. Here we review murine polyomavirus middle T antigen, its mechanisms, and its downstream pathways of transformation. We concentrate on the MMTV-PyMT transgenic mouse, one of the most studied models of breast cancer, which permits the examination of in situ tumor progression from hyperplasia to metastasis.

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“…They discovered that the skin, muscles, and cranial brain were all involved and that the number and size of IHs increased exponentially and were associated with bleeding and anemia, which histologically matched human cavernous IHs. Using SCL-TVA mice and recombinant RCAS/PyMT virus, Sausville [ 74 ] successfully delivered the PyMT virus to endothelial progenitor cells in blood vessels. They discovered that infected mice died quickly from hemorrhagic disease caused by the formation of IH, and this could be because endothelial cells transformed into IH stem cells after being infected with PyMT.…”

Section: Transviral and Genetic Modelsmentioning

confidence: 99%

Infantile hemangioma models: is the needle in a haystack?

Kong

Wang

et al. 2023

J Transl Med

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Infantile hemangioma (IH) is the most prevalent benign vascular tumor in infants, with distinct disease stages and durations. Despite the fact that the majority of IHs can regress spontaneously, a small percentage can cause disfigurement or even be fatal. The mechanisms underlying the development of IH have not been fully elucidated. Establishing stable and reliable IH models provides a standardized experimental platform for elucidating its pathogenesis, thereby facilitating the development of new drugs and the identification of effective treatments. Common IH models include the cell suspension implantation model, the viral gene transfer model, the tissue block transplantation model, and the most recent three-dimensional (3D) microtumor model. This article summarizes the research progress and clinical utility of various IH models, as well as the benefits and drawbacks of each. Researchers should select distinct IH models based on their individual research objectives to achieve their anticipated experimental objectives, thereby increasing the clinical relevance of their findings.

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RCAS/SCL-TVA Animal Model Allows Targeted Delivery of Polyoma Middle T Oncogene to Vascular Endothelial Progenitors In vivo and Results in Hemangioma Development

Cited by 9 publications

References 45 publications

Combined Blockade and Akt/Mtor Pathway Inhibits Growth of Human Hemangioma via Downregulation of Proliferating Cell Nuclear Antigen

Combined Blockade and Akt/Mtor Pathway Inhibits Growth of Human Hemangioma via Downregulation of Proliferating Cell Nuclear Antigen

Lessons in Signaling and Tumorigenesis from Polyomavirus Middle T Antigen

Infantile hemangioma models: is the needle in a haystack?

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