Development of an invivo system to model breast cancer metastatic organotropism and evaluate treatment response using the chick embryo.

Abstract

Metastatic lesions produced through the process of systemic tumor cell dissemination and growth at distant sites are challenging to treat and the primary cause of patient mortality. Developing invivo models of metastasis with utility in evaluating molecular targets and therapeutics in a timely manner would expedite the path to therapeutic discovery. Here, we evaluated breast cancer metastasis and metastatic organotropism using the chick embryo. We developed a method to evaluate metastasis using the MDA231 cell line. Then, using cell lines with demonstrated tropism for the bone, brain, and lung, we evaluated organotropism. Rapid and robust organ-specific metastasis was modeled in the chick embryo and, importantly, recapitulated metastatic organotropism congruent to what has been demonstrated in mice. Treatment response in the metastatic setting was also evaluated and quantified. This work establishes the chick embryo as a model for studies aimed at understanding organotropism and therapeutic response in the metastatic setting.