A Novel Model of Dormancy for Bone Metastatic Breast Cancer Cells

Abstract

Mortality of patients with breast cancer is due overwhelmingly to metastatic spread of the disease. Although dissemination is an early event in breast cancer, extended periods of cancer cell dormancy can result in long latency of metastasis development. Deciphering the mechanisms underlying cancer cell dormancy and subsequent growth at the metastatic site would facilitate development of strategies to interfere with these processes. A challenge in this undertaking has been the lack of models for cancer cell dormancy. We have established novel experimental systems that model the bone microenvironment of the breast cancer metastatic niche. These systems are based on 3D cocultures of breast cancer cells with cell types predominant in bone marrow. We identified conditions in which cancer cells are dormant and conditions in which they proliferate. Dormant cancer cells were able to proliferate upon transfer into supportive microenvironment or upon manipulation of signaling pathways that control dormancy. These experimental systems will be instrumental for metastasis studies, particularly the study of cellular dormancy. Cancer Res; 73(23); 6886-99. Ó2013 AACR.

Evaluation of chemotherapeutics in a three-dimensional breast cancer model

“…In addition, expanding 3D cell culture models to study the impact of co-culture on metastatic sites around the body in a format suitable for screening would be highly beneficial. Recent advances in developing selected models have been made, but their use in compound screening has not been evaluated (Marlow et al 2013).…”

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

“…910 and 920 magnification of histological sections of tumour-bearing bone discs isolated from animals at 8 and 10 weeks. As indicated, human breast cancer cells were visualized following staining using an antibody specific for COX4, mouse-derived vessels using mouse anti-CD31, humanderived vessels using human anti-CD31, and macrophage infiltration using an antibody to F4/80 models have been successfully used to investigate direct interactions between breast cancer cells and other cell types within bone (osteoblasts and mesenchymal cells) [29,30] they lack faithful anatomical reconstruction of the metastatic site and are unable to mimic the ''vicious cycle'' between tumour cells and bone cells that is driven by resorption of the bone matrix. Previously, laboratories have used mouse calvaria seeded with breast cancer cells to model the vicious cycle.…”

Human Bone Xenografts: from Preclinical Testing for Regenerative Medicine to Modeling of Diseases

“…It is anticipated that such efforts will have significant impact on refining the current xenograft models by reproducing the heterocellular composition of the bone marrow, which, in turn, are expected to have profound effects on cancer cell behavior [109,110].…”