Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma

Zhongyun Dong, Rakesh Kumar, Xiulan Yang, Isaiah J. Fidler

Research output: Contribution to journalArticle

437 Citations (Scopus)

Abstract

To determine the mechanism responsible for the in vivo production of angiostatin that inhibits growth and metastasis in Lewis lung carcinoma (3LL), we implanted 3LL valiant cells into the subcutis of syngeneic C57BL/6 mice. The tumors were infiltrated by macrophages and expressed high levels of steady-state mRNA for metalloelastase (MME). Successive passages (more than three) of cultures established from the tumors resulted in complete depletion of macrophages; steady-state MME mRNA, elastinolytic activity, and production of angiostatin (in the presence of plasminogen) were correspondingly reduced. Coculture of macrophages with either 3LL cells or their conditioned media containing granulocyte-macrophage colony-stimulating factor resulted in secretion of MME and production of angiostatin by the macrophages, suggesting that angiostatin is produced by tumor-infiltrating macrophages whose MME expression is stimulated by tumor cell-derived granulocyte-macrophage colony- stimulating factor.

Original languageEnglish (US)
Pages (from-to)801-810
Number of pages10
JournalCell
Volume88
Issue number6
DOIs
StatePublished - Mar 21 1997

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Matrix Metalloproteinase 12
Angiostatins
Lewis Lung Carcinoma
Macrophages
Tumors
Messenger RNA
Granulocyte-Macrophage Colony-Stimulating Factor
Neoplasms
Plasminogen
Conditioned Culture Medium
Coculture Techniques
Inbred C57BL Mouse
Cells
Neoplasm Metastasis
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. / Dong, Zhongyun; Kumar, Rakesh; Yang, Xiulan; Fidler, Isaiah J.

In: Cell, Vol. 88, No. 6, 21.03.1997, p. 801-810.

Research output: Contribution to journalArticle

Dong, Zhongyun ; Kumar, Rakesh ; Yang, Xiulan ; Fidler, Isaiah J. / Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. In: Cell. 1997 ; Vol. 88, No. 6. pp. 801-810.
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