L'hormone antimüllérienne (AMH)et son utilité clinique

L'AMH est exprimée par les gonades et joue un rôle important dans la différentiation sexuelle masculine et la fonction gonadique. Le dosage de l'AMH est utilisé pour évaluer la présence de tissus testiculaires chez des patients pédiatriques présentant une anomalie du développement sexuel. En médecine de la reproduction, l'AMH est utilisée comme marqueur de la réserve ovarienne, pour prédire la réponse à la stimulation ovarienne pour fécondation in vitro et détecter les patientes à risque de mauvaise réponse à la stimulation. L'AMH circulante est également étudiée pour le diagnostic du syndrome des ovaires polykystiques et dans le contexte de traitements chirurgicaux ou médicaux pouvant altérer la réserve ovarienne

Linking cell-surface GRP78 to cancer: From basic research to clinical value of GRP78 antibodies

Glucose-related protein 78 (GRP78) is a chaperone protein localized primarily in the endoplasmic reticulum (ER) lumen, where it helps in proper protein folding by targeting misfolded proteins and facilitating protein assembly. In stressed cells, GRP78 is translocated to the cell surface (csGRP78) where it binds to various ligands and triggers different intracellular pathways. Thus, csGRP78 expression is associated with cancer, involved in the maintenance and progression of the disease. Extracellular exposition of csGRP78 leads to the production of autoantibodies as observed in patients with prostate or ovarian cancer, in which the ability to target csGRP78 affects the tumor development. Present on the surface of cancer cells and not normal cells in vivo, csGRP78 represents an interesting target for therapeutic antibody strategies. Here we give an overview of the csGRP78 function in the cell and its role in oncogenesis, thereby providing insight into the clinical value of GRP78 monoclonal antibodies for cancer prognosis and treatment

Factors regulating trophoblast invasion

Implantation in the human is unique. This uniqueness is characterized on the maternal side by a spontaneous and massive decidualization of the endometrium and on the embryonic side by an almost unlimited invasive potential. Human embryos express an intrinsic invasive potential, which allows them to implant almost anywhere except in the endometrium because it protects itself from implantation. Human implantation is thus only possible during a limited period of time known as the implantation window. This mini review stresses the importance of studying trophoblast invasion into the endometrium as a model for human implantation. Cytotrophoblastic cells (CTB) can easily be isolated from first-trimester legal abortions and retain their invasive behavior when cultured in vitro. This model shows that matrix metalloproteinases (MMPs) are produced by CTB and are instrumental to their invasive behavior. Embryo implantation and tumor invasion use these same biochemical mediators for invasion. However, in contrast to tumor invasion, trophoblast invasion is limited both in time and space: it occurs during the first trimester of pregnancy and invasion does not go beyond the proximal third of the myometrium. Factors regulating MMP expression are of maternal and fetal origin

PEDF gene therapy in ovarian cancer

Ovarian cancer-associated ascites is generally considered non-beneficial for disease status. However, our group was able to identify PEDF in the acellular fraction of ascites, which shows antiangiogenic and proapoptotic effects on tumor cells. Thus, we propose inducing PEDF gene expression using the Sleeping Beauty transposon (SBT) system may potentially emerge as a new therapeutic tool in ovarian cancer treatment

An active product of cruciferous vegetables, 3,3'-diindolylmethane, inhibits invasive properties of extravillous cytotrophoblastic cells

During implantation, human trophoblastic cells have to proliferate, migrate and invade pregnant uterus. A natural product of cruciferous vegetables, 3,3'-diindolylmethane (DIM), is known to induce some stress response genes (such as glucose-regulated protein 78 kDa (GRP78)) and to have anti-invasive and pro-apoptotic effects on tumor cells. Therefore, we have investigated the potential effect of DIM on invasive extravillous cytotrophoblasts (evCTBs) cells

Heat shock proteins in ovarian cancer: a potential target for therapy

Ovarian cancer is the leading cause of death from gynecologic cancer in Western countries. Most of the patients are chemosensitive, and they will present a complete response after initial treatment, but most of them will relapse within 2 years. The resistance to standard chemotherapy represents a significant clinical challenge. Therefore, a better understanding of the molecular mechanisms involved in the drug resistance should allow to improve the treatment in this disease. Interestingly, recent data showed essential roles of heat shock proteins (HSPs) in various processes of carcinogenesis and their association with resistance to anticancer drugs. Here, we report the main investigations on HSPs in ovarian cancer with specific emphasis on clinical application

Role of Par-4 in GRP78 Translocation

GRP78 is a classical endoplasmic reticulum (ER)-localized protein, acting as a chaperone and master regulator of the unfolding protein response in this location. Interestingly, under certain conditions, GRP78 is also located at the cell surface. More concretely, it was observed at the cell surface of several types of cancer cells, but also of trophoblastic cells and stressed cells in general. Cell surface GRP78 can bind to extracellular proteins and promote the activation of different signaling pathways. One of these proteins is prostate apoptosis response 4 (Par-4), a pro-apoptotic protein which is secreted by cancer cells. It was observed that the secretion of Par-4 was increased in parallel with GRP78 cell-surface localization, suggesting a relationship between these events. In this review, we discuss the role of Par-4 in GRP78 relocation at the cell surface