
Inhibition of Tumor Cell Invasion by Ubenimex (Bestatin) in vitro
Author(s) -
Saiki Ikuo,
Murata Jun,
Watanabe Kunihito,
Fujii Hideji,
Abe Fuminori,
Azuma Ichiro
Publication year - 1989
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1989.tb01729.x
Subject(s) - matrigel , aminopeptidase , in vitro , basement membrane , cancer research , cell , mechanism of action , biology , cancer cell , melanoma , lewis lung carcinoma , microbiology and biotechnology , metastasis , biochemistry , cancer , leucine , genetics , amino acid
We have investigated the effect of the immunomodulator ubenimex (bestatin) on tumor cell invasion of reconstituted basement membrane (Matrigel). The invasion of B16‐BL6 melanoma cells and Lewis lung carcinoma (3LL) cells into Matrigel‐coated filters was inhibited by the presence of bestatin in a concentration‐dependent manner. The prctrcatment of either tumor cells or Matrigel with bestatin, however, had little effect on the invasion of tumor cells. Since bestatin was found to inhibit aminopeptidase in addition to its immunomodulating activities, the inhibition of tumor invasion by bestatin is likely to be associated with the action as an enzyme inhibitor. Other aminopeptidase inhibitors, arphamcnine B and amastatin A, could also inhibit tumor cell invasion into Matrigel. Bestatin inhibited hydrolyzing activities towards substrates of aminopeptidases in B16‐BL6 melanoma cells. However, bestatin did not have any effect on the haptotactic migration and adhesion of tumor cells to the substrates. These results indicated that bestatin may inhibit tumor cell invasion through a mechanism involving its inhibitory action on aminopeptidases in tumor cells.