The role of Il-34 in the pathogenesis of osteosarcoma

Kristina Schiavone and Dominique Heymann

May 2019

Osteosarcoma (OS) is the most common malignant primary bone tumour occurring in children and adolescents. Owing to an aggressive local growth pattern, and a high predisposition to metastasize this disease has an unfavourable prognosis and is one of the leading causes of paediatric cancer associated death. Overall survival of OS patients has remained unchanged over the past 30 years highlighting the need for a better characterization of the disease and new therapeutic strategies. A key modulator in the pathogenesis of OS is the tumour niche. This is a specialised microenvironment that promotes the emergence of tumour initiating cells and provides favourable conditions for their growth and development. IL-34 is a novel cytokine with roles in bone development and the biology of bone sarcomas. IL-34 shares a common receptor with the macrophage colony stimulating factor (M-CSF), and both IL-34 and M-CSF signal through the macrophage colony stimulating factor receptor (MCSF-R). Both mediate the biology of mononuclear phagocytic cells and polarize macrophages into immunosuppressive M2 type. In osteosarcoma, IL-34 has been identified as promoting progression by increasing the tissue vasculature and stimulating the recruitment of macrophages. Consequently, IL-34 appears as a pro-metastatic regulator in osteosarcoma. Understanding the key roles of IL-34 in bone development and in the pathogenesis of OS by targeting the M-CSF/IL-34/M-CSFR triad, represents promising therapeutic approaches for OS.

Kristina Schiavone

Kristina Schiavone is a PhD student at the department of Oncology and Metabolism at the University of Sheffield with an MSc in Molecular Medicine. Her research is directed at understanding the biological functions of the cytokine Interleukin (IL)-34 and its contribution to the pathogenesis of osteosarcoma. She hopes that her study will lead to the improvement of current therapies and development of individualised treatments for osteosarcoma patients.

Dominique Heymann

Professor Dominique Heymann is head of the European Associated Laboratory “Sarcoma Research Unit”, Inserm at the University of Nantes (France) and the University of Sheffield (UK). His main research topics are the pathogenesis of bone sarcomas, with particular interest in the dialog of bone microenvironment and tumour cells. His research aims to improve the knowledge on sarcomas to develop new therapeutic approaches.