Multifaceted Functions of Prokineticins in Reproductive Cancers and Proposed Associated Therapies

Author(s): Constance Collet, Roland Abi Nahed, Kevin Gemy, Wael Traboulsi, Nicolas Lemaitre, Pierre-Adrien Bolze, Pascale Hoffmann, Mohamed Benharouga, Nadia Alfaidy

Prokineticin 1 and prokineticin 2 are two secreted proteins that belong to the prokineticin family. The two ligands act via two G protein-coupled receptors, PROKR1 and PROKR2 to induce cell’s proliferation, migration, invasion and permeability. They mostly act on epithelial, endothelial and immune cells. Deregulations in the expression of the ligands and/or the receptors of this family have been associated with both tumor and non-tumor pathologies of the reproductive system. In these pathologies, prokineticins have been reported to be associated with strong angiogenic and inflammatory activities. While their direct involvement in some threatening reproductive non-tumor pathologies such as kallmann syndrome, polycystic ovaries, preeclampsia and fetal growth restriction are well established, their role and their consideration as potential targets in the tumors of the reproductive system are stil debated. This review will address the multifaceted roles of prokineticins and their receptors in reproductive cancers. Especially, the review will address the role of the prokineticin system in two female cancers, the ovarian cancer and the gestational cancer, Choriocarcinoma. The two types of cancer differentially express the prokineticin ligands at their early developmental stages, leading to different overall responses to be adapted when antagonisation of the prokineticin system is proposed. The review will summarize recent advances in the understanding of the prokineticin system’s involvement in the reproductive cancers, discuss its multifaceted roles in relation to prokineticin’s actions and proposes associated therapies.