A preclinical mouse model of hepatic metastasis to instruct effective treatment modalities

Preclinical mouse models mimicking human diseases instruct the design and validation of novel therapeutic opportunities. In the case of cancer, genetically engineered mouse models of autochthonous tumors and models based on the orthotopic or heterotopic transplant of syngeneic or xenogeneic tumor cells have driven research to date. In the case of metastatic disease, fewer models exist, hindering the testing of appropriate therapies. This represents a severe limitation, especially for those diseases that lack evident clinical manifestations and often reveal as metastatic at the time of first diagnosis. For these patients the development of new treatments is needed. Here, we describe a protocol allowing to study hepatic metastasis of mouse and human pancreas adenocarcinoma, an unmet clinical need. This protocol recapitulates multiple and disseminated metastatic hepatic lesions based on syngeneic or xenogeneic tumor cells portal vein injection. The metastatic spread and the sensitivity to therapy are monitored in longitudinal studies by non-invasive Magnetic Resonance Imaging. Additionally, multiparametric immunohistochemistry allows the tracing of metastasis immune contexture, allowing immune-correlate definition of disease development.