An immunocompetent, multifluorescent resource for real-time analysis of osteosarcoma progression, metastasis, and response to therapy
Abstract
Despite substantial treatment improvements, the 5-year survival rate for metastatic osteosarcoma (OS) is still as low as 20%. Immunocompetent genetic mouse models of OS have been introduced, enabling in vivo OS studies. Here, we present the ROCCIA mouse, a quintuple-mutant extension of these models that develops multifluorescent OS tumors, allowing distinct fluorescently labeled OS cell populations to be identified and traced both within tumors and in the circulation. In addition, this model enables postnatal inactivation of the p53 and Rb1 genes, thus resembling development and progression of OS in humans. Using this model, we show that osterix (Osx)-expressing fluorescent tumor cells appear in circulation upon OS development and predominate in lung metastases, thus representing a potential target for future therapies. We also show that the immunological landscape of this model's tumor microenvironment mimics the previously described human OS microenvironment. Therefore, this immunocompetent, quintuple mutant, multifluorescent mouse model represents a powerful resource to analyze OS tumor development and metastasis in real time and to test translational therapies.
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