Important Initiative Roles of CD44 and Tenascin in Sampson's Theory of the Pathogenesis and Development of Endometriosis

Background Among several theories explaining the pathogenesis of endometriosis, Sampson's theory seems to be the most reliable and popular. However, this theory does have some problems. First, the onset of endometriosis is not as common as retrograde menstruation. Second, the surface of the peritoneum is capable of preventing the adhesion of foreign bodies such as endometrial cells. Regarding the first problem, several studies on immunosurveillance have been reported. The second problems has not yet been clarified, Therefore we investigated the problem in the present report. Methods Levels of CD44 and tenascin in both menstrual and peripheral blood were assayed in 19 healthy volunteer women in the first experiment. In the second experiment, the effects of tenascin on the activity of MMP-9 were investigated, because the invasive ability of endometriotic cells is known to be due to MMP activity. Results CD44 and tenascin concentrations were significantly higher in menstrual blood than in peripheral blood. Since CD44 is a specific hyaluronic acid receptor, CD44 in menstrual blood was demonstrated to be a specific matchmaker of adhesion between the endometrial cells and the peritoneal surface. Tenascin in menstrual blood and endometriotic cells up-regulated MMP activity and promoted the invasive action of endometriotic cells. Conclusion The present study clarified that adhesion of endometrial cells in menstrual blood on adhesion-preventive peritoneal surface was achieved by a mediator, CD44, in menstrual blood and that the ability of endometriotic cells to invade, induced by MMP, was achieved through up-regulation of MMP activity by the mediator tenascin.