Greg Mundy

VI Meeting on Cancer-Induced Bone Disease

This latest international conference on cancer-induced bone diseases, organized by the Cancer and Bone Society, attracted over 300 participants, who considered basic and clinical aspects of the many ways in which cancers affect the skeleton. Previous meetings have developed the theme of the importance of the bone microenvironment in influencing tumor behavior. This was a major topic, with many examples throughout the meeting from basic, translational and clinical aspects of both cancer and bone biology. Cancers of the breast and prostate, and the bone disease multiple myeloma were under the spotlight the most. In all cases there have been major advances in our understanding of the pathogenetic mechanisms, clinical application and appraisal of bone-targeted drugs and the identification of new drug targets.

Abstract 1956: A novel mouse model of breast cancer metastasis to bone

Patients with advanced stage breast cancer develop bone metastasis, which leads to hypercalcemia, fractures, nerve compression, paralysis and pain. Breast cancer bone lesions can be osteolytic or osteoblastic, however osteolytic lesions are predominant. Currently, there is no experimental model available to examine osteotropism or trafficking of breast cancer cells to the bone from the primary tumor. TGFβ signaling has been suggested to be responsible for osteotropism. TGFβ stimulates Gli2 and PTHrP expression, which have been shown to be responsible for osteolysis. We have shown that MCF10A, AT-1 and CA1d human breast epithelial cells are responsive to TGFβ and express very high levels of Gli2 and PTHrP. Orthotopic grafting to the cleared fatpad of SCID mice shows that MCF10A and AT-1 cells do not form tumors, even when grafted with normal fibroblasts. CA1d carcinoma cells that are co-grafted with normal fibroblasts show rapid tumor formation with 100% incidence, whereas CA1d cells grafted alone rarely form tumors in the orthotopic site. The tumors can be localized real-time and non-invasively using optical imaging of GFP. X-ray imaging revealed loss of bone density in sacral/caudal vertebrae and hindlimbs. Ca1d grafts generate undifferentiated primary tumors that metastasize to lung and bone. Future studies will determine if CA1d cells stimulate osteolysis. This model may provide a valuable model to examine osteotropism of breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1956.