Objective: To evaluate the autocrine stimulation hypothesis, primary cultures of malignant and normal endometrium were assayed for differences in response to growth factors (GF) GF and 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-alpha (TGF-alpha), insulin-like GF-I (IGF-1), anti-EGF receptor antibody (Ab528), and anti-IGF-1 receptor antibody (alpha IR3) at physiologic concentrations. Tritiated thymidine incorporation was measured.
Results: Malignant endometrial cells increased thymidine incorporation when incubated with EGF (20.75%), TGF-alpha (19.8%), or IGF-1 (32.8%) compared to untreated control cells. When incubated with Ab528 or alpha IR3 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-alpha (-25.6%), and IGF-1 (31.9%). Incubation of normal cells with Ab528 and alpha IR3 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.