ECTS2016 Poster Presentations Cancer and bone: basic, translational and clinical (37 abstracts)
Clinical and experimental evidence suggest a protective effect of Paget’s disease of bone against skeletal metastasization from solid tumors
Daniela Merlotti 1, , Nadia Rucci 3 , Domenico Rendina 4 , Simone Bianciardi 2 , Isabella Anna Evangelista 2 , Argia Ucci 3 , Stefano Rotatori 2 , Guido Sebastiani 2 , Francesco Dotta 2 , Simone Cenci 1 , Pasquale Strazzullo 4 , Ranuccio Nuti 2 , Anna Teti 3 & Luigi Gennari 2
1Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy; 2Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; 3Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy; 4Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
Paget’s disease of bone (PDB) is a common disorder of bone metabolism characterized by focal areas of excessive and rapid bone resorption and formation, leading to bone pain, deformity and fractures. Despite the well documented increase in the risk of primary bone tumors due to neoplastic degeneration of pagetic tissue, a large retrospective analysis suggested that patients with prostate cancer and PDB have delayed time to bone metastases and improved overall survival than do patients with prostate cancer alone (Br J Cancer 2012;107:646–51). This association is unexpected since metastatic cells seed in skeletal sites under active turnover containing dense marrow cellularity and high bone turnover markers (as typically observed in PDB) have been consistently related with negative clinical outcomes and increased skeletal metastasization from prostate cancer or other solid tumors. Based on this observation, we performed a survey of retrospective clinical databases in 893 patients from the Italian PDB Registry (of whom 79 with documented prostate or breast cancer) and we observed a significantly decreased prevalence of skeletal metastases from both tumors with respect to the estimates from the general population, with a total absence of metastases in the 43 cases with the occurrence of cancer after the diagnosis of PDB, despite a mean observation period of 10.5±4.3 years. Consistent with this observation, in a preliminary in vitro analysis, the conditioned media (CM) from osteoclasts derived from peripheral blood leucocytes of patients with active PDB was able to decrease the proliferation of the osteotropic breast cancer cell line MDA-MB-231, as assessed by the MTT test, with respect to CM of controls. Taken together, these results indicate that PDB patients have a distinct bone condition or a unique bone microenvironment that protects them from bone metastasis and strongly encourage further analyses in order to identify the underlying molecular mechanisms.
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Bone Abstracts
ISSN 2052-1219 (online)
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