Higher expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) and metalloproteinase-9 (MMP-9) in a rat model of peritoneal endometriosis is similar to cancer diseases

Abstract

BackgroundEndometriosis is a common disease characterized by the presence of a functional endometrium outside the uterine cavity, causing pelvic pain, dysmenorrheal, and infertility. This disease has been associated to development of different types of malignancies; therefore new blood vessels are essential for the survival of the endometrial implant. Our previous observations on humans showed that angiogenesis is predominantly found in rectosigmoid endometriosis, a deeply infiltrating disease. In this study, we have established the experimental model of rat peritoneal endometriosis to evaluate the process of angiogenesis and to compare with eutopic endometrium.MethodsWe have investigated the morphological characteristics of these lesions and the vascular density, VEGF and its receptor Flk-1 and MMP-9 expression, and activated macrophage distribution, using immunohistochemistry and RT-PCR.ResultsAs expected, the auto-transplantation of endometrium pieces into the peritoneal cavity is a well-established method for endometriosis induction in rats. The lesions were cystic and vascularized, and demonstrated histological hallmarks of human pathology, such as endometrial glands and stroma. The vascular density and the presence of VEGF and Flk-1 and MMP-9 were significantly higher in endometriotic lesions than in eutopic endometrium, and confirmed the angiogenic potential of these lesions. We also observed an increase in the number of activated macrophages (ED-1 positive cells) in the endometriotic lesions, showing a positive correlation with VEGF.ConclusionThe present endometriosis model would be useful for investigation of the mechanisms of angiogenesis process involved in the peritoneal attachment of endometrial cells, as well as of the effects of therapeutic drugs, particularly with antiangiogenic activity.

Increased Expression of ID2, PRELP, and SMOC2 Genes in Patients with Endometriosis

“…It was previously suggested that, in endometriosis, the proteins from the extracellular matrix might be responsible for disturbance in physiological functions such as endometrial secretion, implantation, and menstruation (22). Other studies found high expression of these proteins in the ectopic endometrium, which could lead to the development of endometriosis (23).…”

The Local Immune Mechanisms Involved in the Formation of Endometriotic Lesions

“…Up to now the prominent changes of MMPs production in animals with experimental endometriosis have been demonstrated. The level of MMP-3 and MMP-9 was significantly higher in endometriotic lesions in rats with experimental endometriosis than in matched eutopic endometrium (Machado et al, 2010;Cox et al, 2001). Suppression of MMP-2 and MMP-9 activity in mice led to the inhibition of endometriosis progression in animals with the decrease of endometriotic lesions weight (Chen et al, 2010).…”

Combination of capecitabine and ludartin inhibits colon cancer growth in mice

“…VEGF plays an important role in the progression of tumour angiogenesis; its expression is a characteristic of angiogenesis [16,17]. Studies have shown that higher expression of VEGF in tumor cells is associated with the development of drug resistance [18][19][20].…”