Measurement of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Blood and Tissues: Clinical and Experimental Applications

Abstract

The balance between production and activation of MMPs and their inhibition by TIMPs is a crucial aspect of cancer invasion and metastasis. On the basis of the concept that MMPs synthesized in tissues seep into the bloodstream, we have examined MMP levels in the plasma of patients with cancer. In colorectal, breast, prostate, and bladder cancer, most patients with aggressive disease have increased plasma levels of gelatinase B. In patients with advanced colorectal cancer, high levels of either gelatinase B or TIMP complex were associated with shortened survival. We propose that these assays may be clinically useful in characterizing metastatic potential in selected kinds of cancer. In rheumatoid arthritis and systemic lupus erythematosus (SLE), serum and plasma levels of stromelysin-1 were approximately 3-5-fold increased. Fluctuating serum stromelysin-1 levels in SLE did not correspond with change in disease activity. In SLE, stromelysin-1 may be a component of the chronic tissue repair process rather than being responsible for inciting tissue damage. On the basis of these observations, we conclude that measurement of plasma/serum MMP and TIMP levels may provide important data for selecting and following patients considered for treatment with drugs that interfere with MMP activity.

Prognostic Significance of Matrix Metalloproteinase 2 and Tissue Inhibitor of Metalloproteinase 2 Expression in Prostate Cancer

“…Analysis of both primary and metastatic tumors has shown increased relative MMP expression at the metastatic site, supporting a role in tumor migration and spread (44). Additionally, increased MMP levels have been reported in the plasma and urine of patients with a variety of advanced malignancies (45). Cancer outcome studies have also shown that increased expression of MMPs is associated with shortened patient survival (10,12,46).…”

Zinc and metalloproteinases 2 and 9: What is their relation with breast cancer?

“…Zucker et al 29 demonstrated that the high expression of MMPs, observed mainly in cancerous processes, is due to changes in gene transcription, with the increase of these enzymes leading to a poor prognosis for various types of cancer. 30,31 A study conducted by Benson et al 32 evaluated the expression of MMPs in different types of tissues with breast cancer and normal tissues.…”

Generation of a recombinant Sendai virus that is selectively activated and lyses human tumor cells expressing matrix metalloproteinases

“…The protease species as well as their levels would be relatively easy to determine by the analysis of biopsy materials from individual patients by conventional immunohistochemistry, ELISA and other assay methods. [39][40][41][42] Once they are determined, it would also be easy to generate appropriate protease activation mutants of SeV and related envelope viruses. The safety of recombinant SeVs is another key issue.…”