MDA-MB-435 human breast carcinoma metastasis to bone

Abstract

Breast cancer metastasizes to bone with high frequency and incidence. However, studies of breast cancer metastasis to bone have been limited by two factors. First, the number of models that colonize bone are limited. Second, detection of bone metastases is too insensitive or too laborious for routine, large-scale studies or for studying the earliest steps in bone colonization. To partially alleviate these problems, the highly metastatic MDA-MB-435 (435) human breast carcinoma cell line was engineered to constitutively express enhanced green fluorescent protein (GFP). While 435GFP cells did not form femoral metastases following orthotopic or intravenous injections, they produced widespread osteolytic skeletal metastases following injection into the left ventricle of the heart. All mice developed at least one femur metastasis as well as a mandibular metastasis. As in humans, osseous metastases localized predominantly to trabecular regions, especially proximal and distal femur, proximal tibia, proximal humerus and lumbar vertebrae. 435GFP cells also developed metastases in adrenal glands, brain and ovary following intracardiac injection, suggesting that this model may also be useful for studying organotropism to other tissues as well. Additionally, GFP-tagging permitted detection of single cells and microscopic metastases in bone at early time points following arrival and at stages of proliferation prior to coalescence of individual metastases.