Team description

Keywords: Primary bone tumor, bone regeneration

Osteosarcoma (OS) and Ewing sarcoma (ES) are the most frequent malignant primary bone tumors that mostly arise in children, adolescents and young adults (bone sarcomas). Current treatment consists of excision of the tumor, associated with a highly toxic chemotherapy. Unfortunately, in many cases, an absence of response to anti-tumor drugs is observed, leading to the development of metastases and patient’s death. Survival is closely correlated to the response of tumor cells to anti-mitotic drugs, reaching 70 % at five years for localized tumors in best series but only 30 % when pulmonary metastases are detected at diagnosis, for patients with relapsed disease or for bad responders to chemotherapy. Whether the cellular component of these primary bone tumors is osteoclastic (case of giant cell tumors) or osteoblastic (case of osteoblastic osteosarcomas), or mesenchymal stem/stromal (case of Ewing sarcomas) the common point between these different tumoral entities is their capacity to deregulate bone remodelling. In fact, the invasion of bony tissue by a primitive or metastatic tumor cell precociously affects the balance between bone resorption and bone formation. This deregulation of osteoclastic-osteoblastic couplings leads to the release of factors initially trapped in the bone matrix, that in turn promote tumor cell proliferation. The bone tumor microenvironment therefore largely controls the growth of the tumor and thus its future. Results obtained by the laboratory have demonstrated the supportive role of mesenchymal stem cells and osteoclasts and the key role of various cytokines or growth factors in the development of osteosarcoma and Ewing sarcoma. The bone tumor microenvironment including non-tumor cells and extracellular matrix thus largely controls the growth of these tumors. In such clinical context, the response of bone sarcomas to chemotherapy being insufficient, it is necessary to better characterize the communications between tumor cells and bone microenvironment (osteoclasts, osteoblasts, mesenchymal stromal/stem cells, endothelial cells etc.) and to identify new alternative or additional therapies to improve the therapeutic response of the tumors.

The research projects of the unit are:

- Characterisation of the tumor microenvironment (signaling pathways, cytokines, cell interactions...)

- Imaging of primary bone tumor and the development of new therapeutic approaches

- Development of relevant and original cellular and preclinical animal models

- Transfer to the clinics, thanks to close collaborations with national (GSF-GETO, SFCE) and European (EuroEWING) networks.

Expertises / technical competence

Expertises

• Menchymal stromal/stem cells culture and differentiation.
• Bioprinting of tumors and MSC.
• 2D and 3D cellular models of osteosarcoma and Ewing sarcoma
• Animal models of osteosarcoma and Ewing sarcoma (syngenic, xenografts, PDX, orthotopic induction)

Collaborations

National partnerships :

- GDR MicroNIT (CNRS)

- GDR Biopolymar (IFREMER/Univ Nantes/Univ Paris V)

- "Sarcome Français" group (Gouin F./Rédini F.)

- "Pathologistes Osseux" french group (De Pinieux G)

- « société française des cancers de l’enfant et de l’adolescent » (F. Rédini)

European Partnerships:

- European orthounion project (Layrolle P.)

- EuroEWING network (Rédini F.)

International Partnerships:

- Ronzoni Institute (Milan, Italie)

- Pavia University (Pavia, Italie)

- Rizzoli Orthopaedic Institute (Bologne, Italie)

- St Vincent’s Institute (Melbourne, Australie)

- Leiden University Medical Center (Pays bas)

- Institute of Medical Sciences (Aberdeen, Grande Bretagne)

- Harvard Medical School (USA) - Michigan University (USA)

INSERM UMR_S 1238

Faculté de Médecine

1 rue Gaston Veil

44035 Nantes cedex 1

France