Stimulatory effects of EGF and TGF-α on invasive activity and 5′-deoxy-5-fluorouridine sensitivity in uterine cervical-carcinoma SKG-IIIB cells
✍ Scribed by Masatsugu Ueda; Minoru Ueki; Yoshito Terai; Akira Morimoto; Hideji Fujii; Keiko Yoshizawa; Tomoko Yanagihara
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- French
- Weight
- 110 KB
- Volume
- 72
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
We investigated the effects of epidermal growth factor (EGF) and transforming growth factor(TGF)-␣ on migration, invasion and matrix metalloproteinase (MMP) expression of uterine cervical-carcinoma SKG-IIIb cells, and whether these growth factors affect pyrimidine-nucleoside-phosphorylase(PyNPase) activity and 5Ј-deoxy-5-fluorouridine(5Ј-dFUrd) sensitivity of tumor cells. Tumor-cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were stimulated by 0.1 to 100 ng/ml of EGF and TGF-␣ in a concentration-dependent manner. The zymography of tumor-conditioned medium showed that the treatment of tumor cells with EGF and TGF-␣ resulted in an increase of the 92-kDa type-IV collagenase (MMP-9), which was confirmed by immunoblot analysis. These growth factors also up-regulated the expression of PyNPase activity of tumor cells and consequently enhanced the anti-proliferative action of 5Ј-dFUrd, a cytostatic that is biotransformed to 5-fluorouracil (5-FUra) by PyNPase. However, EGF and TGF-␣ did not have significant effects on the 5-FUra sensitivity of tumor cells. These results suggest that EGF and TGF-␣, tumor environmental factors, simultaneously up-regulate the potential of uterine cervical-carcinoma cells to invade extracellular matrices and their PyNPase activity, which are subsequently associated with the specific action of 5Ј-dFUrd selectively killing tumor cells of gynecological origin with high invasive and metastatic potential. Int.