Evaluation of metastatic burden and recovery of human metastatic cells from a mouse model

Metastatic dissemination is the major cause of death in cancer. Xenotransplantation of tumor tissue into immunodeficient mice is a widespread preclinical technique to study tumor development. However, preclinical studies on the spreading of metastases were so far hampered by the poor dissemination of malignant human tumors in conventional immunodeficient hosts, like the nude mouse. The development of highly immunodeficient knockout mice spurred a new wave of metastatic model systems. It was recently shown that human HER-2-positive breast cancer cells, which do not metastasize in nude mice, when implanted in knockout mice with severe immunodeficiency, give rise to multiorgan metastatic patterns resembling those observed in human patients. The growth of metastatic nodules in a variety of locations, including brain, lungs, liver, kidneys, adrenals, ovaries, and bone marrow, opens up the problem of quantifying metastatic burden and recovering human metastatic cells from mouse organs for cellular and molecular studies in vitro .Here we used the Mouse Cell Depletion Kit (Miltenyi Biotec) to enrich and quantify metastatic human cells, derived from human breast carcinoma, in a model of brain metastases1 in NOD scid gamma (NOD.Cg- Prkdc scid Il2rg tm1Wjl/SzJ, NSG) mice.