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 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.
Reynolds
R K
RK
Division of Gynecologic Oncology, University of Michigan Hospitals, Ann Arbor 48109-0718, USA.
Owens
C A
CA
Roberts
J A
JA
D000906:Antibodies / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D017978:Receptors, Growth Factor / Q000276:immunology; D012016:Reference Values; D013936:Thymidine / Q000378:metabolism
D000906:Antibodies; D006133:Growth Substances; D017978:Receptors, Growth Factor; D013936:Thymidine