Tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line, KKLS, in the chick embryo

Yuri Tsuchiya, Hiroshi Sato, Yoshio Endo, Yasunori Okada, Masayosi Mai, Takuma Sasaki, Motoharu Seiki

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Abstract

Tissue inhibitors of metalloproteinases (TIMPs) are the negative regulators of matrix metalloproteinases that degrade extracellular matrix. We examined the regulatory role of TIMP-1 in the metastatic activity of human gastric cancer cell lines in chick embryos because unregulated matrix metalloproteinase activities are belived to be essential during metastatic processes. One of the nine cell lines examined, KKLS cells, formed metastatic colonies in the chick livers. These cells expressed undetectable levels of TIMP-1, and this was not inducible by 12-O-tetradecanoylphorbol 13-acetate. Derivatives of KKLS cells with different levels of TIMP-1 expression were prepared by transfection of the human TIMP-1 complementary DNA controlled by a simian virus 40 early promoter. Metastatic abilities were suppressed by almost 70% in the transfectants expressing high levels of TIMP-1. In contrast, no suppression was observed in the control transfectants or in cells expressing the transfected TIMP-1 gene at low levels. These data indicate that a reduced expression of TIMP-1 in KKLS cells is responsible for their consequent metastatic potential. Moreover, it suggests that matrix metalloproteinase enzymatic activities are a prerequisite for metastatic activity in this experimental model system.

Original languageEnglish
Pages (from-to)1397-1402
Number of pages6
JournalCancer Research
Volume53
Issue number6
Publication statusPublished - 1993 Mar 15

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Tissue Inhibitor of Metalloproteinase-1
Chick Embryo
Stomach Neoplasms
Cell Line
Matrix Metalloproteinases
Tissue Inhibitor of Metalloproteinases
Simian virus 40
Tetradecanoylphorbol Acetate
Human Activities
Extracellular Matrix
Transfection
Theoretical Models
Complementary DNA
Liver
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line, KKLS, in the chick embryo. / Tsuchiya, Yuri; Sato, Hiroshi; Endo, Yoshio; Okada, Yasunori; Mai, Masayosi; Sasaki, Takuma; Seiki, Motoharu.

In: Cancer Research, Vol. 53, No. 6, 15.03.1993, p. 1397-1402.

Research output: Contribution to journalArticle

Tsuchiya, Y, Sato, H, Endo, Y, Okada, Y, Mai, M, Sasaki, T & Seiki, M 1993, 'Tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line, KKLS, in the chick embryo', Cancer Research, vol. 53, no. 6, pp. 1397-1402.
Tsuchiya, Yuri ; Sato, Hiroshi ; Endo, Yoshio ; Okada, Yasunori ; Mai, Masayosi ; Sasaki, Takuma ; Seiki, Motoharu. / Tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line, KKLS, in the chick embryo. In: Cancer Research. 1993 ; Vol. 53, No. 6. pp. 1397-1402.
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