TY - JOUR
T1 - Down-regulation of TIMP-1 inhibits cell migration, invasion, and metastatic colonization in lung adenocarcinoma
AU - Chang, Ying Hua
AU - Chiu, Yi Jen
AU - Cheng, Hung Chi
AU - Liu, Fang Ju
AU - Lai, Wu Wei
AU - Chang, Hsiao Jen
AU - Liao, Pao Chi
N1 - Publisher Copyright:
© 2015, International Society of Oncology and BioMarkers (ISOBM).
PY - 2015/5/28
Y1 - 2015/5/28
N2 - 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.
AB - 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.
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U2 - 10.1007/s13277-015-3039-5
DO - 10.1007/s13277-015-3039-5
M3 - Article
C2 - 25578494
AN - SCOPUS:84929955323
VL - 36
SP - 3957
EP - 3967
JO - Oncodevelopmental Biology and Medicine
JF - Oncodevelopmental Biology and Medicine
SN - 1010-4283
IS - 5
ER -