Identification and Characterization of Extracellular Matrix Metalloproteinase Inducer in Human Endometrium during the Menstrual Cyclein Vivoandin Vitro

Abstract

Extracellular matrix metalloproteinase inducer (EMMPRIN) participates in the breakdown of the extracellular matrix (ECM) by augmenting matrix metalloproteinase (MMP) expression. In the present study, we identified and characterized the menstrual cycle-dependent expression of EMMPRIN in human endometrium in vivo. At the proliferative phase of the menstrual cycle, EMMPRIN was detected in glandular epithelium of the basal layer in endometrium. In addition, at the superficial region of the functional layer, EMMPRIN was expressed in stroma but not glandular epithelium. At the secretory phase, EMMPRIN was found in both stroma and glandular epithelium of the functional layer and glandular epithelium of the basal layer. Furthermore, EMMPRIN colocalized with MMP-1/collagenase-1 in the glandular epithelium in vivo. Western blot analysis of tissue from the functional layer showed that EMMPRIN species with molecular weights of approximately 35 and 47 kDa were detected at the proliferative phase, whereas approximately 35- and 51-kDa EMMPRIN species were predominantly expressed at the secretory phase. In addition, the variant EMMPRIN molecules were found to differ in glycosylation. On the other hand, EMMPRIN was constitutively produced in primary cultured endometrial stromal and glandular epithelial cells. The production and glycosylation of EMMPRIN in the stromal cells were augmented by progesterone at the posttranscriptional and posttranslational stages, respectively. These results suggest for the first time that EMMPRIN is expressed in human endometrium during the menstrual cycle and that its expression and glycosylation are augmented by progesterone. Moreover, EMMPRIN may be involved in ECM breakdown at the interface between endometrial cells and ECM by using EMMPRIN-bound MMP-1.

High incidence of EMMPRIN expression in human tumors

“…Differential modification of EMMPRIN through glycosylation may be cell-type specific or associated with malignancy of cells. Alternatively, as there is evidence reported in the literature suggesting that posttranslational modification of EMM-PRIN might be regulated by hormones, 44 it is tempting to speculate that differential modification of the EMMPRIN polypeptide preferentially may occur in hormone-dependent cell types. However, the mechanisms controlling differential glycosylation of EMMPRIN still remain to be elucidated.…”

Embryo–epithelium interactions during implantation at a glance

“…The laminin receptors α1β1, α6β1 and α7β1 are likely to be important at this stage. Furthermore, the integrin β1 interactor CD147 (EMMPRIN, officially known as basigin) is required for optimal implantation (Igakura et al, 1998;Kuno et al, 1998;Lee et al, 2013;Noguchi et al, 2003;Xiao et al, 2002).…”

A novel functional site of extracellular matrix metalloproteinase inducer (EMMPRIN) that limits the migration of human uterine cervical carcinoma cells

“…EMMPRIN is expressed on the cell surface of various tumors and some normal tissues/cells such as uterine endometrium, macrophages, and T-lymphocytes (1,(3)(4)(5). Many investigators have reported that increased EMMPRIN expression causes the augmentation of matrix metalloproteinases (MMPs)-1, -2, and -3, and membrane-type MMP (MT-MMP) expression in peritumoral stoma cells, and thereby increases tumor invasiveness in vivo and in vitro (6)(7)(8)(9).…”