Differential expression of the α2-macroglobulin receptor and the receptor associated protein in normal human endometrium and endometrial carcinoma

Extracellular matrix degradation, mediated by the activation of receptor-bound proteolytic enzymes, is essential to the process of cellular invasion. Many normal physiological functions such as endometrial remodelling are reliant on the activation of these surface associated proteolytic enzymes, as are pathological functions such as cancer-cell invasion. The internalization of proteolytic complexes is mediated by the multifunctional clearance receptor, alpha(2)-macroglobulin receptor/LRP. The role of LRP and its ligand binding inhibitor, the receptor-associated protein (RAP), in the advancement of invasive endometrial carcinoma is unknown. The aim of this study was to compare the expression of LRP and RAP mRNA in normal endometrium (n = 14) and endometrial carcinoma (n = 33) by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Expression of LRP mRNA in normal endometrium was significantly increased in the secretory phase when compared with proliferative phase endometrium (P < 0.05). The expression of LRP in all carcinomas examined was significantly reduced to about 20% of the amount in normal endometrium (P < 0.05), whereas RAP expression was not significantly different between endometrium and carcinoma. No significant difference in the level of LRP or RAP expression was observed between carcinoma grades or stages. In conclusion, we have shown that LRP expression is differentially regulated in the normal endometrium during the menstrual cycle and is decreased in invasive endometrial carcinomas.