TIMP-2 inhibits metastasis and predicts prognosis of colorectal cancer via regulating MMP-9

Weimin Wang; Dan Li; Liangliang Xiang; Mengying Lv; Li Tao; Tengyang Ni; Jianliang Deng; Xiancheng Gu; Sunagawa Masatara; Yanqing Liu; Yan Zhou

doi:10.1080/19336918.2019.1639303

TIMP-2 inhibits metastasis and predicts prognosis of colorectal cancer via regulating MMP-9

Cell Adh Migr. 2019 Dec;13(1):273-284. doi: 10.1080/19336918.2019.1639303.

Authors

Weimin Wang^{1

2

3}, Dan Li^{1

2

3}, Liangliang Xiang^{1

2}, Mengying Lv^{1

2}, Li Tao^{1

2}, Tengyang Ni^{1

2}, Jianliang Deng³, Xiancheng Gu³, Sunagawa Masatara⁴, Yanqing Liu^{1

2

3}, Yan Zhou^{1

2

3}

Affiliations

¹ a Institute of Traslational Medicine , Medical College, Yangzhou University , Yangzhou , PR China.
² b The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine , Yangzhou , PR China.
³ c Department of Oncology , Yixing Hospital Affiliated to Medical College of Yangzhou University , Yixing , Jiangsu , PR China.
⁴ d Department of Physiology , School of Medicine, Showa University , Tokyo , Japan.

Abstract

Colorectal cancer has a common cause of morbidity and mortality. Therefore, it is urgent to detect reliable biomarkers to predict prognosis in CRC. Here, we determined the expression of TIMP-2 and MMP-9 in a CRC tissue microarray by immunohistochemistry. We found that lower TIMP-2 or/and higher MMP-9 expression in cancer tissues was correlated with poorer overall survival (OS). TIMP-2 or MMP-9 expression was independent prognostic factors for CRC. Furthermore, TIMP-2 and MMP-9 expression had a synergistic role as efficient prognostic indicators for CRC patients. In vitro and in vivo, TIMP-2 could inhibit HCT 116 cells invasion and migration by regulating MMP-9. In sum, a combined expression of TIMP-2 and MMP-9 as efficient prognostic indicators was found for the first time.

Keywords: CRC; MMP-9; TIMP-2; metastasis; prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Biomarkers, Tumor / metabolism*
Cell Line, Tumor
Colorectal Neoplasms / diagnosis
Colorectal Neoplasms / genetics
Colorectal Neoplasms / pathology*
Female
Gene Expression Regulation, Neoplastic / genetics*
HCT116 Cells
Humans
Immunohistochemistry
Male
Matrix Metalloproteinase 9 / metabolism*
Middle Aged
Neoplasm Invasiveness / pathology
Neoplasm Metastasis / pathology
Neovascularization, Pathologic / pathology
Prognosis
Tissue Inhibitor of Metalloproteinase-2 / metabolism*

Substances

Biomarkers, Tumor
TIMP2 protein, human
Tissue Inhibitor of Metalloproteinase-2
MMP9 protein, human
Matrix Metalloproteinase 9

Grants and funding

This work was supported by the National Natural Science Foundation of China [81773944];Natural Science Foundation of Jiangsu Province [BK20180927];the Natural Science Foundation of Jiangsu Province for Youths [BK20170516];Wuxi City Health Planning Commission project [MS201815];Young Medicine Focus Talent Foundation of Jiangsu Province [QNRC2016206];Postgraduate Research by Practice Innovation Program of Jiangsu Province [KYCX18_2382].