Spine Metastases in Immunocompromised Mice after Intracardiac Injection of MDA-MB-231-SCP2 Breast Cancer Cells

SIMPLE SUMMARY: Breast cancer cells typically metastasize to bone, where their interaction with bone remodeling cell types enhances metastatic outgrowth and osteolytic bone destruction. The respective knowledge is largely based on xenograft models, where human breast cancer cells are injected into immunocompromised mice. Importantly, however, whereas skeletal analyses in these animals are usually restricted to hindlimb bones, human skeletal metastases are far more frequent in the spine. Therefore, our study addressed the question, if breast cancer cells injected into immunocompromised mice would also metastasize to the spine, and if this process is influenced by the amount of trabecular bone. We injected an established breast cancer cell line into immunocompromised mice with or without a transgene causing severe osteoporosis. Importantly, we found more tumor cell clusters of different size in spine sections than in femora, but the presence of the transgene did not affect their spreading and metastatic outgrowth. ABSTRACT: Breast cancer cells frequently metastasize to bone, where their interaction with bone remodeling cell types enhances osteolytic bone destruction. Importantly, however, whereas skeletal analyses of xenograft models are usually restricted to hindlimb bones, human skeletal metastases are far more frequent in the spine, where trabecular bone mass is higher compared to femur or tibia. Here, we addressed whether breast cancer cells injected into immunocompromised mice metastasize to the spine and if this process is influenced by the amount of trabecular bone. We also took advantage of mice carrying the Col1a1-Krm2 transgene, which display severe osteoporosis. After crossing this transgene into the immunocompromised NSG background we injected MDA-MB-231-SCP2 breast cancer cells and analyzed their distribution three weeks thereafter. We identified more tumor cells and clusters of different size in spine sections than in femora, which allowed influences on bone remodeling cell types to be analyzed by comparing tumor-free to tumor-burdened areas. Unexpectedly, the Col1a1-Krm2 transgene did not affect spreading and metastatic outgrowth of MDA-MB-231-SCP2 cells, suggesting that bone tumor interactions are more relevant at later stages of metastatic progression.