Prostate cancer-derived exosomes promote osteoblast differentiation and activity through phospholipase D2

This project will focus on the interaction established between exosomes derived from the prostate tumour cell and the osteoblast within the bone microenvironment. This dialogue is essential in the onset and development of bone metastasis in prostate cancer (CaP). In particular, we are seeking to understand the involvement of tumour phospholipase D2 (PLD2), a highly conserved membrane protein present in exosomes, in the dialogue between the tumour cell and the osteoblast. Our research team recently demonstrated the involvement of the PLD1 and PLD2 isoforms in tumour progression in different CaP cell models. We have also demonstrated for the first time the presence of PLD2 in exosomes derived from metastatic prostate cell lines. The presence of PLD2 in these exosomes would determine their capacity to activate differentiation and mineralisation in several osteoblastic models. This project is therefore based on two complementary objectives:

- The first objective is to determinate the molecular mechanisms involving PLD2 in the interaction between exosomes derived from prostate tumour cells and osteoblasts. In particular, we will study how exosomal PLD2 participates in osteoblastic activation and differentiation.

- the second objective is to study whether exosomes derived from prostate tumour cells containing PLD2 are addressed to the bone marrow and induce the appearance and development of bone metastases in mouse models of CaP.

Through this research project, we will support our hypothesis that exosomal PLD2 is a key enzyme in the tumour cell-osteoblast interaction and a potential target molecule in the treatment of CaP bone metastasis.

This work was supported by “Ligue contre le cancer” and Oncostarter.