The response to epidermal growth factor of human maxillary tumor cells in terms of tumor growth, invasion and expression of proteinase inhibitors.
Three cancer cell lines, IMC-2, IMC-3 and IMC-4, were established from a single tumor of a patient with maxillary cancer. We examined responses to epidermal growth factor (EGF) of these 3 cell lines with regard to cell growth and tumor invasion. The growth rate of IMC-2 in nude mice was markedly faster than that of the IMC-3 and IMC-4 cell lines. Assay for invasion through fibrin gels showed significantly enhanced invasive capacity of IMC-2 cells in response to EGF, but no change for IMC-3 and IMC-4 cells. We examined response to EGF of IMC-2 cells with regard to expression of a growth-related oncogene (c-fos), proteinases and their inhibitors. Expression of c-fos was transiently increased in IMC-2 cells at rates comparable to those seen in the 2 other lines in the presence of EGF. There was no apparent effect of EGF on the expression of urokinase-type plasminogen activator and 72-kDa type-IV collagenase in IMC-2 cells. In contrast, EGF specifically enhanced the expression of plasminogen activator inhibitor-I (PAI-I) and tissue inhibitor of metalloproteinases-I (TIMP-I) in IMC-2 cells. Our data suggest that proteinase inhibitors or other related factors may play an important role in tumor growth and invasion in response to EGF.
Mizoguchi
H
H
Dept. of Biochemistry, Oita Medical School, Japan.
Komiyama
S
S
Matsui
K
K
Hamanaka
R
R
Ono
M
M
Kiue
A
A
Kobayashi
M
M
Shimizu
N
N
Welgus
H G
HG
Kuwano
M
M
D000818:Animals; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015870:Gene Expression; D016762:Genes, fos / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008441:Maxillary Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D003012:Microbial Collagenase / Q000378:metabolism; D009368:Neoplasm Transplantation; D015849:Plasminogen Inactivators / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D004815:Epidermal Growth Factor; D003012:Microbial Collagenase