Cultured Endometrial Cancer Cells Exhibit Autocrine Growth Factor Stimulation That Is Not Observed in Cultured Normal Endometrial Cells

Abstract

Objective: To evaluate the autocrine stimulation hypothesis, primary cultures of malignant and normal endometrium were assayed for differences in response to growth factors (GF) and GF receptor blocking antibodies. Methods: Thirteen normal and 10 malignant endometrial samples were collected. Cells were enzymatically dispersed and maintained in serum-free medium. They were incubated with epidermal GF (EGF), transforming GF-α (TGF-α), insulin-like GF-I (IGF-1), anti-EGF receptor antibody (Ab528), and anti-IGF-1 receptor antibody (αIR3) at physiologic concentrations. Tritiated thymidine incorporation was measured. Results: Malignant endometrial cells increased thymidine incorporation when incubated with EGF (20.75%), TGF-α (19.8%), or IGF-1 (32.8%) compared to untreated control cells. When incubated with Ab528 or αIR3 antibodies alone, proliferation of malignant cells was inhibited (−12.4 and −23%, respectively,P< 0.003). Normal endometrial cells were inhibited by EGF (−24.9%), TGF-α (−25.6%), and IGF-1 (31.9%). Incubation of normal cells with Ab528 and αIR3 antibodies stimulated growth (125 and 115%, respectively,P< 0.02). Conclusions: These data are consistent with the autocrine stimulation hypothesis for neoplastic endometrium and illustrate differences compared to nonneoplastic endometrial growth factor-mediated proliferation.