Development and characterization of experimental models of oligometastatic and polymetastatic progression

Clinical oligometastases are characterized by a limited number of metastases which are a form of stable metastatic dissemination that presents the window for curative treatment. A better understanding of the molecular mechanisms underlining the differences between the stable oligometastases from the widespread polymetastases requires the development of clinically-relevant animal models for mechanistic investigation. In this study, we created from a MDA-MB-435 human tumor, the first mouse xenograft model of oligo-and polymetastases. Here, using this novel xenograft model to study two distinct types of metastatic progression, we report detailed characterization of experimental oligo-and polymetastases models. The oligometastatic model remained stable after serial rounds of in vivo passage, had limited organ involvement and had less than 5 discrete metastatic foci. In contrast, the polymetastatic progression model showed multiple metastatic foci in the lung, or involved multiple anatomic sites. In summary, the new xenograft models of metastasis that we reported here recapitulated phenotypic features of two clinically relevant human metastasis phenotypes: the oligometastatic and polymetastatic progression. These models should prove useful for mechanistic investigation as well as for evaluating therapeutic targeting of sustained oligometastases to achieve the clinical goal of long-term disease free survival.