Bone Metastasis Mouse Models And The Vicious Cycle

Only the murine mammary carcinoma 4T1 model spontaneously forms metastases to the bone, but it also spreads to the liver, lungs, and brain (15). Standard bone metastasis models are produced by injecting cancer cells into the left cardiac ventricle of immunocompromised mice (6). Within this model, MDA-MB-231 human breast cancer cells produce osteolytic bone lesions within a month after tumor cell inoculation (6). MDA-MB-435s and BT549 breast cancer cell lines also produce osteolytic lesions (6). Other breast cancer cell lines produce osteoblastic (T47D, MCF-7, ZR75.1) or mixed (BT483) bone lesions within this model (6, 16). These bone metastasis mouse models have led to an understanding of the complex interactions that develop between breast cancer cells and the bone microenvironment that lead to lesion formation and the incurability of the disease (6), although they lack important regulators of cancer progresssion such as T lymphocytes. Data from these models provide evidence that a "vicious cycle" develops between breast cancer cells and the other cells within bone (6). Once breast cancer cells have entered bone, they secrete various factors that act on bone cells and other cells within the bone, causing them to secrete factors back onto the breast cancer cells, driving a "vicious cycle" that renders the disease incurable. Inhibiting the secreted factors may interfere with the vicious cycle and lead to a cure for breast cancer bone metastasis (6).

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