Targeted mutagenesis of Timp-1 reveals that lung tumor invasion is influenced by Timp-1 genotype of the tumor but not by that of the host

Oncogene. 1996 Dec 5;13(11):2307-14.

Abstract

Timp-1 has been implicated as a suppressor of tumor metastasis. To study the relative importance of Timp-1 expression by tumor vs host during tumor invasion, three pairs of co-isogenic, tumorigenic cells containing wild-type or mutant Timp-1 alleles were generated. These were used in experimental metastasis assays in wild-type or Timp-1-deficient mice. Timp-1 expression in tumorigenic cells could either increase or decrease tumor invasion of lungs in a tumor cell-specific manner. This suggests that depending on the tumor, Timp-1 can either suppress or potentiate metastasis. Mice deficient for Timp-1 were indistinguishable from wild-type mice in metastasis assays with all tumorigenic cells tested. Although Timp-1 is a secreted protein, and lung produces other Timps, the influence of Timp-1 on lung invasion by the tumorigenic cells tested is cell-autonomous, depending only on Timp-1 genotype of tumor and not that of host.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Genotype
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mutagenesis, Site-Directed
  • Neoplasm Invasiveness / genetics
  • Tissue Inhibitor of Metalloproteinases
  • Tumor Cells, Cultured

Substances

  • Glycoproteins
  • Tissue Inhibitor of Metalloproteinases