Platelet-derived growth factor promotes endometrial epithelial cell proliferation

OBJECTIVE: Our purpose was to determine the effects of platelet-derived growth factor on the proliferation of endometrial epithelial cells. Platelet-derived growth factor and its receptors have been identified in the endometrium, and platelet-derived growth factor is a mitogen for endometrial stromal cells. Released from macrophages and platelets at sites of ectopic endometrial growth, platelet-derived growth factor could promote the progression of endometriosis and endometrial cancer. STUDY DESIGN: Endometrial epithelail cell lines were developed from proliferative-phase endometria from two patients without endometrial lesions. Cell lines were confirmed to be epithelial. Proliferation assays were conducted on both lines with recombinant human platelet-derived growth factor-AA, AB, and BB. Assays were also performed at different doses, times, and cell densities with platelet-derived growth factor-AB. RESULTS: All isoforms of platelet-derived growth factor were potent mitogens for both endometrial epithelial cell lines. The greatest proliferative responses were achieved at 10 ng/ml and at 24 hours. Responses decreased significantly in confluent cultures. CONCLUSIONS: These results suggest that endometrial epithelial cells have functional platelet-derived growth factor-α receptors that signal cell replication. The greater activity of platelet-derived growth factor in subconfluent cultures may indicate that receptor numbers or affinity are up-regulated when cell-cell contact is disrupted. These data support a role for platelet-derived growth factor in normal endometrial proliferation and in pathologic proliferation such as endometriosis and endometrial cancer.