Comparative studies of tissue inhibitor of metalloproteinases-1 in plasma, serum and tumour tissue extracts from patients with primary colorectal cancer

Abstract

The lack of correlation between tumour tissue TIMP-1 and blood levels of TIMP-1 suggests that other sources than the tumour tissue itself may contribute to the increased levels of plasma TIMP-1 in patients with colorectal cancer. However, degradation of cell membranes, rapid secretion into the blood stream and other factors may be responsible for the observed lack of association between TIMP-1 concentrations in blood and tumour tissue extracts.

Diagnostic significance of TIMP-1 level in serum and its immunohistochemical expression in colorectal cancer patients

“…Furthermore, Baker et al [17] noted that the growth of TIMP-1 in tumor homogenates was closely connected with Duke's cancer stage, lymph node involvement and MMP-1 level. The protein level in tissue homogenates of the tumor in all the reports mentioned above was significantly lower than its plasma concentration [19]. Based on the findings of the tissue analysis, the researchers conducted the experiments on other material as well.…”

“…According to the studies conducted by the author, activated or damaged platelets are the source of the TIMP-1 protein, which means that the protein may also be derived from other cellular elements. Sorensen et al [19] analyzed the level of TIMP-1 protein in plasma, serum and tissue extracts collected from patients with primary CRC. The authors of this study observed an increase in the level of TIMP-1 in the serum compared to the plasma of patients with CRC.…”

Banking of Biological Fluids for Studies of Disease-associated Protein Biomarkers

“…When comparing TIMP-1 levels between different plasma types, we obtained very consistent results when comparing EDTA and citrate plasma samples obtained simultaneously from the same individual, whereas heparin plasma gave variable results (17). When analyzing the level of TIMP-1 in plasma and serum from healthy individuals and from patients, we have observed that serum consistently contains higher values and that these values fluctuate as compared with plasma, which has very stable and reproducible TIMP-1 levels (18). The main explanation for this observation most probably is that because TIMP-1 is stored in the ␣-granules of platelets it will be released from these cells during ex vivo coagulation when platelets are activated (19).…”

Effective Treatment of Advanced Colorectal Cancer by Rapamycin and 5-FU/Oxaliplatin Monitored by TIMP-1

“…21,22,36 In this study, treatment with rapamycin caused nearly complete disappearance of TIMP-1 in tumor tissue samples. Because TIMP-1 has broad tumorpromoting activity (pro-angiogenesis, anti-apoptosis; promotion of cell growth and proliferation), one could speculate that its down-regulation by rapamycin could be another mechanism through which rapamycin mediates its antitumor effects.…”

“…The tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) has been shown to correlate with disease stage and tumorigenicity of colorectal cancer 20,21 (and reviewed in 22 ). TIMP-1 shares homology with its three other family members, and all display a robust sensitivity to changes in pH, temperature, and denaturing conditions due to their disulphide bonds.…”