Human breast cancer cells induce angiogenesis, recruitment, and activation of osteoclasts in osteolytic metastasis

Purpose: The purpose of this study was to elucidate the potential of human breast cancer cells (BCC) to induce matrix degradation and neo-vascularization, essential for continued tumor growth, in osteolyric lesions. Methods: BCC were inoculated into the left cardiac ventricle of female athymic mice and osteolytic lesions were radiologically visualized within 4 weeks from inoculation. Results: Histomorphometric analysis of bone sections revealed a significant increase in the number and maturity of osteoclasts (OCl) lining the bone surfaces next to tumor tissue when compared to corresponding bone surfaces in healthy mice. In addition, a large number of newly formed blood vessels could be visualized by immunohistochemistry at the periphery of and within tumor tissue. When bone marrow (BM) cells were cultured in the presence of BCC the OCl formation was increased threefold. These OCl were also found to be more mature and to have greater resorptive activity. Moreover, BCC were found to stimulate proliferation, migration, and differentiation of BM-derived endothelial cells. Conclusions: Matrix destruction and neo-vascularization are accomplished by BCC arrested in the BM cavity by increasing recruitment and activity of OCl and by induction of angiogenesis within or in proximity to the tumor tissue.