CULTURED ENDOMETRIAL CANCER-CELLS EXHIBIT AUTOCRINE GROWTH-FACTOR STIMULATION THAT IS NOT OBSERVED IN CULTURED NORMAL ENDOMETRIAL CELLS

Objective: To evaluate the autocrine stimulation hypothesis, primary c ultures of malignant and normal endometrium were assayed for differenc es in response to growth factors (GF) and GF receptor blocking antibod ies. Methods: Thirteen normal and 10 malignant endometrial samples wer e collected. Cells were enzymatically dispersed and maintained in seru m-free medium. They were incubated with epidermal GF (EGF), transformi ng GF-alpha (TGF-alpha), insulin-like GF-I (IGF-1), anti-EGF receptor antibody (Ab528), and anti-IGF-1 receptor antibody (alpha IR3) at phys iologic concentrations. Tritiated thymidine incorporation was measured . Results: Malignant endometrial cells increased thymidine incorporati on 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 a lpha IR3 antibodies alone, proliferation of malignant cells was inhibi ted (-12.4 and -23%, respectively, P < 0.003). Normal endometrial cell s 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 stim ulated growth (125 and 115%, respectively, P < 0.02). Conclusions: The se data are consistent with the autocrine stimulation hypothesis for n eoplastic endometrium and illustrate differences compared to nonneopla stic endometrial growth factor-mediated proliferation. (C) 1996 Academ ic Press, Inc.