“…Because extracellular matrix remodeling is the major activity of a family of enzymes known as matrix metalloproteinases (MMPs), these enzymes have come under investigation for their contributions to the malignant phenotype [43, 44]. Matrix metalloproteinase MMP-2, MMP-7 and MMP-9, regulated by tissue inhibitor of metalloproteinases TIMP-2, TIMP-7 and TIMP-9, respectively, play important roles in the degradation of the basement membrane during tumor invasion [25, 30, 43, 44]. The activities of MMP-2 and loss of balanced expressions of MMP-2/TIMP-2 and MMP-9/TIMP-1 are suggested as playing important roles in invasive growth related to the gross type of cholangiocarcinoma [45].…”