Down-regulation of TIMP-1 inhibits cell migration, invasion, and metastatic colonization in lung adenocarcinoma

Tissue inhibitor metalloproteinase-1 (TIMP-1) is clinically associated with a poor prognosis for various cancers, but the roles of TIMP-1 in lung cancer metastasis are controversial. Our previous secretomic study revealed that TIMP-1 is highly abundant in high invasiveness cells of lung adenocarcinoma. In the current study, TIMP-1 abundances in primary lung adenocarcinoma tissues, as revealed by immunohistochemistry, are significantly higher in patients with lymph invasion and distant metastasis than in those without. Receiver operating characteristic curve analyses suggest 73.7 and 86.2 % accuracy to separate patients with lymph node and distant metastasis and those without, respectively. Moreover, we demonstrate that the expression level of TIMP-1 positively associates with cell mobility, invasiveness, and metastatic colonization. Most notably, the novel mechanism in which TIMP-1 facilitates metastatic colonization through the mediation of pericellular polyFN1 assembly was revealed. In summary, this study presents novel functions of TIMP-1 in promoting cancer metastasis and suggests TIMP-1 is a potential tissue biomarker for lymph invasion and distant metastasis of lung adenocarcinoma.