Biological implications of growth factors on the mechanism of invasion in gynecological tumor cells.
We investigated the effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on migration, invasion and proteinase expression of gynecological cultured cancer cells (SKG-IIIb cervical squamous cell carcinoma, OMC-4 cervical adenocarcinoma, SNG-M endometrial adenocarcinoma and OMC-3 ovarian adenocarcinoma), and whether these growth factors affect thymidine phosphorylase/platelet-derived endothelial cell growth factor expression of tumor cells. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. The zymography of tumor-conditioned medium showed that the treatment of tumor cells with EGF and TGF-alpha resulted in the increase of type IV collagenases, stromelysin and urokinase-type plasminogen activator which was partly confirmed by immunoblot analysis. The expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor which has angiogenic activity, was also upregulated by these growth factors. These results suggest that EGF and TGF-alpha act as positive regulators on the invasion process of gynecological tumor cells which may be associated with their stimulatory action on the motility of tumor cells, the expression of proteinases secreted by tumor cells and the angiogenic phenotype.
Ueda
M
M
Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
Ueki
M
M
Terai
Y
Y
Ueki
K
K
Kumagai
K
K
Fujii
H
H
Yoshizawa
K
K
Nakajima
M
M
D000230:Adenocarcinoma / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002465:Cell Movement; D016889:Endometrial Neoplasms / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005833:Genital Neoplasms, Female / Q000473:pathology*; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000473:pathology; D013939:Thymidine Phosphorylase / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000473:pathology
D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D013939:Thymidine Phosphorylase; D014568:Urokinase-Type Plasminogen Activator; D008666:Metalloendopeptidases