IDENTIFICATION OF A TRANSFORMING GROWTH-FACTOR-BETA-1 ACTIVATOR DERIVED FROM A HUMAN GASTRIC-CANCER CELL-LINE

被引:32
作者
HORIMOTO, M [1 ]
KATO, J [1 ]
TAKIMOTO, R [1 ]
TERUI, T [1 ]
MOGI, Y [1 ]
NIITSU, Y [1 ]
机构
[1] SAPPORO MED UNIV,SCH MED,DEPT INTERNAL MED 4,CHUO KU,SAPPORO,HOKKAIDO 060,JAPAN
关键词
TRANSFORMING GROWTH FACTOR BETA-1; TRANSFORMING GROWTH FACTOR BETA-1 ACTIVATOR; GASTRIC CANCER;
D O I
10.1038/bjc.1995.393
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
It has been shown that some types of tumour cells produce activated transforming growth factor beta-1 (TGF-beta 1). However, the mechanism for the activation of TGF-beta 1 derived from tumour cells has not been fully elucidated. The present study was undertaken to characterise an activator of latent TGF-beta 1 secreted from a human gastric cancer cen line, KATO-III. Western blot analyses using antibodies for TGF-beta 1, latency associated peptide (LAP) and latent TGF-beta 1-binding protein (LTBP) revealed that, in the cell lysate of KATO-III, TGF-beta 1 protein was expressed as a small latent complex of TGF-beta 1 and LAP. This was also confirmed by a gel chromatographic analysis of the cell lysate obtained from KATO-III. A 2.5 kb transcript of TGF-beta 1 mRNA was detected in KATO-III cells by Northern blot analysis. A gel chromatographic analysis of the conditioned medium from KATO-III cells revealed, in addition to the active form of TGF-beta 1, a factor which activated latent TGF-beta 1 from NRK-49F cells at fractions near a molecular size of 65 000. This factor was inactivated by heat (100 degrees C), acidification, trypsin and serine protease inhibitors. TGF-beta 1 activity in KATO-III cell lysate was not detected in the untreated state, but potent TGF-beta 1 activity was detected after acid treatment. These results suggest that KATO-III releases not only a latent TGF-beta 1 complex but also a type of serine protease, different from plasmin, plasminogen activator, cathepsin D, endoglycosidase F or sialidase, which activates the latent TGF-beta 1 complex as effectively as acid treatment.
引用
收藏
页码:676 / 682
页数:7
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