Sørensen Nanna Møller, Schrohl Anne Sofie, Jensen Vibeke, Christensen Ib Jarle, Nielsen Hans Jørgen, Brünner Nils
Section of Biomedicine, Department of Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark.
Scand J Gastroenterol. 2008;43(2):186-91. doi: 10.1080/00365520701491355.
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.
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).
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.
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.
我们最近发现，术前血浆金属蛋白酶组织抑制因子-1（TIMP-1）水平与结直肠癌患者的预后显著相关。此外，我们还表明，血浆TIMP-1的检测可提供有关特异性和敏感性的信息，可用于结直肠癌的早期检测。然而，尚不清楚结直肠癌患者血浆TIMP-1水平升高是否源于肿瘤组织本身，在肿瘤组织中，TIMP-1主要由位于癌细胞附近的基质细胞表达。本研究的目的是探讨结直肠癌患者血液TIMP-1水平与肿瘤组织TIMP-1水平之间的关联。
采用TIMP-1 ELISA法检测49例结直肠癌患者术前的EDTA血浆、枸橼酸盐血浆和血清以及肿瘤组织提取物中的总TIMP-1水平（非复合和复合TIMP-1）。
49份肿瘤提取物中TIMP-1的中位水平为18.7 ng/mg蛋白（范围3.5-152.0 ng/mg蛋白）。EDTA血浆中TIMP-1的中位值为133.5 ng/ml（范围58.1-559.0 ng/ml），枸橼酸盐血浆中为130.2 ng/ml（范围57.0-572.0 ng/ml），血清中为207.2 ng/ml（范围72.6-828.0 ng/ml）。肿瘤提取物中的TIMP-1含量与血液中的TIMP-1含量之间未发现显著相关性。然而，EDTA和枸橼酸盐血浆中的TIMP-1水平（r=0.75；p<0.0001）以及EDTA血浆和血清中的TIMP-1水平（r=0.64；p<0.0001）高度相关。
肿瘤组织TIMP-1与血液中TIMP-1水平缺乏相关性，提示结直肠癌患者血浆TIMP-1水平升高可能并非源于肿瘤组织本身，而是其他来源。然而，细胞膜的降解、快速分泌入血流以及其他因素可能导致血液中TIMP-1浓度与肿瘤组织提取物之间缺乏关联。
