Preclinical Mouse Intraductal Model (MIND) to Study Metastatic Dormancy in Estrogen Receptor-Positive Breast Cancer.

Abstract

Here, we describe a clinically relevant xenograft model of hormone receptor-positive breast cancer that maintains estrogen receptor (ER) status without the need for exogenous supplementation of hormones. The naturally low 17-β-estradiol levels in host mice recapitulate levels seen in post-menopausal women. By introducing breast cancer cells directly into their "natural" microenvironment of the milk ducts, these cells maintain hormone receptor status, model the clinical progression of the disease, and develop ER- metastatic lesions or dormant micrometastatic lesions in the case of ER+ BC. With the use of GFP/RFP:Luc2 reporters, we can monitor in vivo tumour growth and conduct ex vivo metastases assays to evaluate dormant metastatic cell harboring organs. Upon recovery of metastatic cells from ER+ breast cancer models, downstream analyses can be conducted to assess the relationship between epithelial plasticity and metastatic dormancy.