Abstract 2255: In vivo study of serum cancer biomarkers and pain-induced bone metastasis of human prostate tumor in Nude rats

Abstract

Abstract Bone is one of the most frequent sites of spread for many cancers such as breast, prostate, lung or kidney. Management of metastatic bone disease and associated pain can control the symptoms and prevent further complications such as the decrease of quality of life, pathological fracture or compression of the spinal cord. Until recently, investigation of novel drugs in the treatment of cancer-induced bone pain was hampered by a lack of suitable models. The aim of this study was to characterize biochemical markers and behavioral pain responses in an experimental animal model of bone metastases induced by intracardiac injection of PC-3 human prostate cancer cells in Nude rats. Firstly, potential differences of nociceptive responses between healthy Nude rats (classically used in cancer studies) and healthy SD rats (routinely used in pain studies) were assessed in 2 mechanical tests (electronic Von Frey and paw pressure tests) and 2 thermal tests (plantar and acetone tests). Pharmacological response to morphine was also assessed in both strains using the paw pressure test. Secondly, Nude rats were intracardiacally inoculated with PC3 cancer cells or RPMI medium and nociceptive responses were measured between tumor-bearing and non tumor-bearing Nude rats. Behavioral tests were carried out once a week during 4 consecutive weeks. In a satellite group, 15 days after tumor cell injection, 5 Nude rats received 4 intravenous injections of paclitaxel (5 mg/kg every 4 days). Development of bone metastases was monitored by ELISA quantification of serum biomarkers such as CTX-1 and TRACP 5b (bone resorption) and PINP (bone formation). Nociceptive tests in healthy SD and Nude rats did not demonstrate any major difference of hypersensitivity between both strains. Morphine (3 mg/kg, s.c.) induced a similar and classically observed analgesic effect in both strains. Any significant difference between Nude rats inoculated or not with cancer cells was observed neither in mechanical nor in thermal hyperalgesia assays. CTX-1 and TRACP-5b levels were significantly higher in tumor-bearing Nude rats than in non tumor-bearing ones. PINP level was lower in Nude rats injected with PC-3 cells than in non injected-rats. Paclitaxel significantly increased the life span of tumor-bearing Nude rats (ILS > 120%) and affected the kinetic of the 3 serum biomarkers. At sacrifice, CTX-1 and TRACP-5b serum levels were decreased by 51% and 95% respectively, and PINP level was increased by 325% compared to the non-treated rats. These results indicated that intracardiac injection of PC-3 human prostate cancer cells in Nude rats associated with bone formation/resorption serum biomarkers monitoring is a useful experimental in vivo model for bone metastases study and anti-cancer drug evaluation. Surprisingly, pain induced by experimental bone metastases was not demonstrated in this model with classical painful assays. 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 2255.