Comparative studies of tissue inhibitor of metalloproteinases-1 in plasma, serum and tumour tissue extracts from patients with primary colorectal cancer.
OBJECTIVE
We have recently shown that preoperative plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) levels are significantly associated with prognosis of colorectal cancer patients. In addition, we have shown that measurement of plasma TIMP-1 yields information on specificity and sensitivity, which could be used for early detection of colorectal cancer. However, it is not clear whether the increased plasma TIMP-1 levels in colorectal cancer patients are derived from the tumour tissue itself in which it is mainly expressed by the stromal cells located in the vicinity of the cancer cells. The purpose of this study was to examine the association between blood TIMP-1 levels and tumour tissue TIMP-1 levels in colorectal cancer patients.


METHODS
Preoperative EDTA plasma, citrate plasma and serum, as well as tumour tissue extracts from 49 colorectal cancer patients were measured with a TIMP-1 ELISA that measures total TIMP-1 levels (non-complexed and complexed TIMP-1).


RESULTS
The median TIMP-1 level in the 49 tumour extracts was 18.7 ng/mg proteins (range 3.5-152.0 ng/mg protein). The median TIMP-1 value was 133.5 ng/ml (range 58.1-559.0 ng/ml) in EDTA plasma, 130.2 ng/ml (range 57.0-572.0 ng/ml) in citrate plasma and 207.2 ng/ml (range 72.6-828.0 ng/ml) in serum. No significant correlations were found between TIMP-1 content in the tumour extracts and in blood.However, EDTA and citrate plasma TIMP-1 levels (r=0.75; p <0.0001) as well as EDTA plasma and serum TIMP-1 levels (r= .064; p<0.0001) were highly correlated.


CONCLUSIONS
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.
Sørensen
Nanna Møller
NM
Section of Biomedicine, Department of Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark.
Schrohl
Anne Sofie
AS
Jensen
Vibeke
V
Christensen
Ib Jarle
IJ
Nielsen
Hans Jørgen
HJ
Brünner
Nils
N
D000925:Anticoagulants; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D001800:Blood Specimen Collection / Q000379:methods; D019343:Citric Acid; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004492:Edetic Acid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D010949:Plasma; D012680:Sensitivity and Specificity; D044967:Serum; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood* / Q000378:metabolism
D000925:Anticoagulants; D014408:Biomarkers, Tumor; D019715:Tissue Inhibitor of Metalloproteinase-1; D019343:Citric Acid; D004492:Edetic Acid