ECTS Abstracts (2015) 1 P119

The Activity of Everolimus in a Coculture Model of Breast Cancer and Bone Cells

Laura Mercatali1, Alessandro De Vita1, Chiara Spadazzi1, Chiara Liverani1, Federico La Manna1, Yibin Kang2, Alberto Bongiovanni1, Marianna Ricci1, Nada Riva1, Dino Amadori1 & Toni Ibrahim1

1Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 2Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.

Metastatic bone disease has a major impact on both morbidity and mortality of breast cancer patients. Osteolytic lesions are the most common form of bone metastases from breast cancer and are characterised by a significant bone disruption due to a marked increase in osteoclasts number and activity. Alterations in mTOR signalling are involved both in cancer progression and in osteoclasts differentiation. The aim of this study is to highlight the role of mTOR inhibitor everolimus on osteoclastogenesis induced by growth factors or cancer cells media and on cancer cells. We developed an in vitro human model of osteoclastogenesis from peripheral blood monocytes. We used the conditioned media of the osteotropic human breast cancer cell line SCP2. Everolimus was tested at an early step of osteoclastogenesis (5-7 days) and later at 10-12 days of differentiation. Osteoclastogenesis was detected by TRAP assay at day 14. Everolimus was shown to inhibit cancer cells survival of 20%; furthermore SCP2 was able to induce osteoclastogenesis in a significantly statistical manner respect to control. The osteoclast number observed were similar to that obtained with growth factors (differential medium: DM). Everolimus significantly decreased osteoclastogenenis in presence of both conditioned (CM) or (DM). Interestingly, the effect of everolimus was higher if administered to cells early. In this case the inhibition of osteoclastogenesis reached almost the 70%. Finally, with this study we aimed to develop an in vitro model that reproduce the interactions between breast cancer cells and the bone microenvironment. In particular, we found a different effect on osteoclast differentiation according to the timing of Everolimus treatment. This drug, interestingly, had an effect on both cancer cells and bone cells. Our model may represent a valid platform for preclinical trials of bone targeted drugs and for the study of molecular mechanisms beyond breast cancer interplay with bone cells.

Disclosure: The authors declared no competing interests.