Human breast cancer bone metastasis in vitro and in vivo: a novel 3D model system for studies of tumour cell-bone cell interactions

摘要: Bone is established as the preferred site of breast cancer metastasis. However, precise mechanisms responsible for this preference remain unidentified. In order to improve outcome patients with advanced and skeletal involvement, we need better understand how process initiated regulated. As bone metastasis cannot be easily studied in patients, researchers have date mainly relied on vivo xenograft models. A major limitation these that they do not contain a human microenvironment, increasingly considered an important component metastases. address shortcoming, developed novel humanised model, where 1 × 105 luciferase-expressing MDA-MB-231 or T47D tumour cells are seeded viable subchaodral discs vitro. These functional osteoclasts 2-weeks after vitro culture positive staining calcine 1-week demonstrating active resorption/formation. inoculation colonised cores remained <4 weeks, however, use matrigel enhance adhesion moving platform increase diffusion nutrients provided no additional advantage. Following colonisation by cells, pre-seeded were implanted subcutaneously into NOD SCID mice, growth monitored using imaging up 6 weeks. Tumour progressed 80 % animals mimicking later stages Immunohistochemical PCR analysis revealed growing resulted acquiring molecular phenotype previously associated grown showed increased expression IL-1B, HRAS MMP9 decreased S100A4, whereas, DKK2 FN1 unaltered compared same mammary fat pads mice discs.