Do SPY1 overexpressing brain tumors in mice recapitulate features of actual human glioblastomas?

Standing

Undergraduate

Type of Proposal

Oral Presentation

Faculty

Faculty of Science

Faculty Sponsor

Dr. Lisa Porter

Proposal

Animal models offer a platform to study diseases afflicting humans, including malignancies impacting organs such as the brain. In selecting an animal model, a desired feature is that it recapitulates, with fidelity, the human disease condition in question. Here we have undertaken an assessment of a mouse model of glioblastoma in which the gene SPY1 was overexpressed using genetic engineering methods. SPY1 is a cell cycle protein that activates cyclin dependent kinases and thus promotes progression through the cell cycle. Increases in its cellular abundance have been associated with increased aggressiveness in several human cancers, including those of the brain. We therefore hypothesize that SPY1-overexpressing glioblastoma tumours in mice will share features with aggressive brain tumors naturally arising in humans. This study seeks to explore aspects of the degree to which tumors, arising in mouse brains from injected cells overexpressing SPY1, recapitulate glioblastomas that have arisen in human patients. Using computer-assisted microscopic techniques to assess tumor cell proliferation and tumor-host aspects such as vascularity and immune cell distribution, our present comparison is mainly between the mentioned mouse features and those of human glioblastomas as documented in the published literature. This work will importantly shed light on the suitability of this animal model for possible future projects aimed at developing targeted therapies against a very lethal human disease.

Location

Windsor

Grand Challenges

Viable, Healthy and Safe Communities

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Do SPY1 overexpressing brain tumors in mice recapitulate features of actual human glioblastomas?

Windsor

Animal models offer a platform to study diseases afflicting humans, including malignancies impacting organs such as the brain. In selecting an animal model, a desired feature is that it recapitulates, with fidelity, the human disease condition in question. Here we have undertaken an assessment of a mouse model of glioblastoma in which the gene SPY1 was overexpressed using genetic engineering methods. SPY1 is a cell cycle protein that activates cyclin dependent kinases and thus promotes progression through the cell cycle. Increases in its cellular abundance have been associated with increased aggressiveness in several human cancers, including those of the brain. We therefore hypothesize that SPY1-overexpressing glioblastoma tumours in mice will share features with aggressive brain tumors naturally arising in humans. This study seeks to explore aspects of the degree to which tumors, arising in mouse brains from injected cells overexpressing SPY1, recapitulate glioblastomas that have arisen in human patients. Using computer-assisted microscopic techniques to assess tumor cell proliferation and tumor-host aspects such as vascularity and immune cell distribution, our present comparison is mainly between the mentioned mouse features and those of human glioblastomas as documented in the published literature. This work will importantly shed light on the suitability of this animal model for possible future projects aimed at developing targeted therapies against a very lethal human disease.