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Stimulatory effects of EGF and TGF‐α on invasive activity and 5′‐deoxy‐5‐fluorouridine sensitivity in uterine cervical‐carcinoma SKG‐IIIB cells
Author(s) -
Ueda Masatsugu,
Ueki Minoru,
Terai Yoshito,
Morimoto Akira,
Fujii Hideji,
Yoshizawa Keiko,
Yanagihara Tomoko
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970917)72:6<1027::aid-ijc18>3.0.co;2-1
Subject(s) - carcinoma , cervical carcinoma , medicine , cancer research , pathology , biology , endocrinology , oncology , cervical cancer , cancer
We investigated the effects of epidermal growth factor (EGF) and transforming growth factor(TGF)‐α 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 5′‐deoxy‐5‐fluorouridine(5′‐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‐α in a concentration‐dependent manner. The zymography of tumor‐conditioned medium showed that the treatment of tumor cells with EGF and TGF‐α 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 5′‐dFUrd, a cytostatic that is biotransformed to 5‐fluorouracil (5‐FUra) by PyNPase. However, EGF and TGF‐α did not have significant effects on the 5‐FUra sensitivity of tumor cells. These results suggest that EGF and TGF‐α, 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 5′‐dFUrd selectively killing tumor cells of gynecological origin with high invasive and metastatic potential. Int. J. Cancer 72:1027–1033, 1997. © 1997 Wiley‐Liss, Inc.