Matrix metalloproteinase-9 (92 kDa gelatinase/type IV collagenase) from U937 monoblastoid cells

Correlation with cellular invasion

Hideto Watanabe, Isao Nakanishi, Kyoko Yamashita, Taro Hayakawa, Yasunori Okada

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

The role of matrix metalloproteinase-9 (MMP-9, 92 kDa gelatinase/type IV collagenase) in invasion of mononuclear phagocytes was studied with U937 monoblastoid cells. 12-o-tetradecanoyl 13-phorbol acetate (TPA) differentiated them to macrophage-like cells with induction of MMP-9, and tumor necrosis factor α (TNFα) and interleukin-1α (IL-1α) stimulated the production of MMP-9 by TPA-treated cells. TNFα also induced the production of MMP-9 by TPA-untreated U937 cells without morphological differentiation. Other agents including dimethyl sulfoxide (DMSO), all-trans-retinoic acid (all-trans-RA), platelet-derived growth factor and 3′;5′-cyclic monophosphate had no effects on MMP-9 production by TPA-treated or -untreated cells, but all-trans-RA and DMSO did have a morphological effect on the differentiation of the cells. These data suggest that MMP-9 production by U937 cells is regulated by a mechanism independent of the differentiation to macrophage-like cells. MMP-9 was purified to homogeneity as an inactive zymogen with Mr 92,000 (proMMP-9) from TPA-differentiated U937 cells treated with TNFα. ProMMP-9 was activated by p-aminophenylmercuric acetate (APMA) generating an active species of Mr 67,000. Trypsin and cathepsin G also attained activation of the zymogen to its full activity obtained by APMA activation, but plasmin, leukocyte elastase, thrombin and plasma kallikrein had no ability to activate it. APMA-activated MMP-9 degraded type I gelatin readily and cleaved native collagen types III, IV and V. Invasion assays using reconstituted basement membrane coupled with a type IV collagenolysis assay showed good correlations between invasiveness, type IV collagenolysis and proMMP-9 production. Invasion was significantly inhibited by EDTA, α2-macroglobulin and tissue inhibitor of metalloproteinases-1, but not by inhibitors of cathepsin G and leukocyte elastase. These data suggest that MMP-9 plays an important role in the invasion of mononuclear phagocytes through basement membranes.

Original languageEnglish
Pages (from-to)991-999
Number of pages9
JournalJournal of Cell Science
Volume104
Issue number4
Publication statusPublished - 1993 Apr

Fingerprint

U937 Cells
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Acetates
Cathepsin G
Leukocyte Elastase
Enzyme Precursors
Tumor Necrosis Factor-alpha
Phagocytes
Dimethyl Sulfoxide
Tretinoin
Basement Membrane
Macrophages
Collagen Type V
Plasma Kallikrein
Macroglobulins
Tissue Inhibitor of Metalloproteinase-1
Collagen Type III
Collagen Type IV
Fibrinolysin

Keywords

  • Invasion
  • Matrix metalloproteinase
  • Mononuclear phagocytes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Matrix metalloproteinase-9 (92 kDa gelatinase/type IV collagenase) from U937 monoblastoid cells : Correlation with cellular invasion. / Watanabe, Hideto; Nakanishi, Isao; Yamashita, Kyoko; Hayakawa, Taro; Okada, Yasunori.

In: Journal of Cell Science, Vol. 104, No. 4, 04.1993, p. 991-999.

Research output: Contribution to journalArticle

Watanabe, H, Nakanishi, I, Yamashita, K, Hayakawa, T & Okada, Y 1993, 'Matrix metalloproteinase-9 (92 kDa gelatinase/type IV collagenase) from U937 monoblastoid cells: Correlation with cellular invasion', Journal of Cell Science, vol. 104, no. 4, pp. 991-999.
Watanabe, Hideto ; Nakanishi, Isao ; Yamashita, Kyoko ; Hayakawa, Taro ; Okada, Yasunori. / Matrix metalloproteinase-9 (92 kDa gelatinase/type IV collagenase) from U937 monoblastoid cells : Correlation with cellular invasion. In: Journal of Cell Science. 1993 ; Vol. 104, No. 4. pp. 991-999.
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