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.

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.