Novel murine mammary epithelial cell lines that form osteolytic bone metastases: effect of strain background on tumor homing.

摘要: We have developed a series of novel mammary epithelial cell lines from tumors arising in strain 129 mice, with the ultimate goal evaluating role host factors development bone metastases. Mammary were induced mice subcutaneously implanted medroxyprogesterone acetate (MPA) pellets followed by administration DMBA oral gavage. tumor was efficient and independent osteopontin (OPN) expression. Epithelial isolated these tumors; surprisingly, cells did not form upon inoculation into fat pad syngeneic even when MPA present. One OPN-deficient line selected for further study; full transformation required expression both polyoma middle T activated ras. These doubly transfected cells, 1029 GP+Er3, grew soft agar, formed hormone-independent efficiently that spontaneously metastasized to several tissue sites but bone. Derivatives lung metastasis (r3T r3L, respectively): more rapidly than parental GP+Er3 cells. Upon left ventricle injection, r3T r3L osteolytic metastases few seen other organs. filled marrow cavity, caused extensive destruction cortical trabecular Intriguingly, an alternative host, (129× C57Bl/6) F1, on x-ray; instead liver present indicating genetic two strains regulate homing distribution during metastasis. provide important new tool study metastasis, particularly elucidating lesions, as mouse is frequently used manipulations mouse.