Matrix metalloproteinase-2 and tissue inhibitor of metallo-proteinase-2 in colorectal carcinoma invasion and metastasis.
OBJECTIVE
To explore the relationship between matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the development of colorectal carcinoma and to provide a valuable marker for clinical diagnosis.


METHODS
Twenty-five patients with colorectal carcinoma underwent surgical resection. Samples were taken from tumor sites and normal tissues. MMP-2 activity was determined by gelatin zymography. Western blot and ABC immunohistochemical staining were used to detect the expression levels of MMP-2 and TIMP-2 in normal and colorectal carcinoma tissues. Statistical analyses were performed using the Student's t test and one-way ANOVA. P<0.05 was considered statistically significant. All the statistical analyses were performed using SPSS 10.0 software.


RESULTS
MMP-2 activity could be detected in both normal and colorectal carcinoma tissues. MMP-2 activity in colorectal carcinoma tissues was much higher than that in normal tissues (P<0.05, t = 3.916, 4.227). MMP-2 activity was positively related to the colorectal carcinoma invasion depth, lymph node metastasis and Duke's stage. Western blot and ABC immunohistochemical staining demonstrated that the expression level of MMP-2 in colorectal carcinoma tissues was much higher than that in normal tissues (P<0.05, t = 9.429), but the expression level of TIMP-2 in colorectal carcinoma tissues was much lower than that in normal tissues (P<0.05, t = 7.329). The MMP-2/TIMP-2 ratio of colorectal carcinoma was much higher than that of normal tissues. With the progression of invasion depth, lymph node metastasis and tumor Duke's stage, the activity and expression level of MMP-2 and TIMP-2 gradually increased, but the MMP-2/TIMP-2 ratio gradually decreased.


CONCLUSIONS
The balance between MMP-2 and TIMP-2 plays a crucial role in the process of colorectal carcinoma invasion and metastasis.
Li
Bing-Hui
BH
Department of Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China.
Zhao
Peng
P
Liu
Shi-Zheng
SZ
Yu
Yue-Ming
YM
Han
Mei
M
Wen
Jin-Kun
JK
D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2