Abstract 5325: Localized tumor growth in bone: Quantification of tumor burden, bone destruction, and weight-bearing capability in MDA-MB-231 human mammary carcinoma xenograft-bearing immunodeficient rats

Abstract

Abstract Metastatic bone disease is common in multiple myeloma, breast, prostate, and lung cancer patients and is a frequent cause of morbidity in advanced disease. Metastatic bone tumors destroy bone and cause severe bone remodeling which leads to structural weakening and bone fractures and often results in severe bone pain in a large percentage of patients. These studies examined tumor growth, bone erosion, and pain in a nude rat model. A surgical defect was created in the tibia, exposing the marrow cavity. Luciferase-expressing MDA-MB-231 mammary tumor cells were injected into the exposed bone cavity. Rats inoculated with tumor cells were treated with either doxorubicin (3 mg/kg/week, iv) or risedronate (80 ug/kg/day, ip). Animals were monitored weekly for tumor burden by optical imaging and for bone erosion by CT. In addition to clinical observations, weight bearing was measured using an incapacitance tester with separate force transducers for each hind paw. Compared to controls, rats treated with doxorubicin demonstrated a significant decease in luminescence, indicating tumor growth inhibition (bone protection). Decreased luminescence correlated with sparing of the bone as measured by CT. In contrast, the bisphosphonate, risedronate, had limited effect on tumor growth, but preserved bone integrity. In both treatments, protection of bone was associated with normalization of weight-bearing. This finding supports the premise that pain in metastatic bone cancer is attributable to bone loss (destruction) and remodeling. Weight-bearing data correlated directly with clinical observations This model, leveraging multiple imaging modalities, enables longitudinal and quantitative assessment of tumor growth; bone loss, remodeling and sparing, and weight-bearing in test animals that provides a sensitive and robust screening tool to evaluate compounds for anti-tumor, bone-sparing and pain amelioration effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5325. doi:10.1158/1538-7445.AM2011-5325