Tissue inhibitor of metalloproteinase‐1 levels in plasma from tumour arteries and veins of patients with rectal cancer

Abstract

Objective. Tissue inhibitor of metalloproteinase‐1 (TIMP‐1) plays a major role in the regulation of tissue growth, including cancer growth. The TIMP‐1 protein can be determined in plasma, and increased plasma levels of TIMP‐1 are associated with a poor prognosis of colorectal cancer patients. The aim of the present study was to evaluate whether tumour tissue release of the TIMP‐1 protein contributes to the increased plasma levels of TIMP‐1 observed in patients with colorectal cancer. Material and methods. Preoperative blood samples from a peripheral vein and intraoperative blood samples from a tumour artery, a tumour vein and from a peripheral vein were drawn from 24 patients undergoing elective, intended curative surgery for primary rectal cancer. TIMP‐1 levels were determined concurrently in plasma from all samples using a validated ELISA method. Counts of white blood cells and platelets were also carried out. Results. No significant differences between plasma TIMP‐1 levels could be demonstrated in any compartment. In particular, there was no significant difference in TIMP‐1 levels in plasma from tumour arteries and tumour veins. However, there was a significant decrease in neutrophil cell counts from tumour arteries to tumour veins (p<0.001). Conclusions. The present results do not support the current hypothesis that tumour cells contribute substantially to increased plasma TIMP‐1 levels observed in patients with colorectal cancer.

• Colorectal neoplasm
• metalloproteinases
• neutrophils
• surgery
• tissue inhibitor of metalloproteinases‐1

Acknowledgements

We thank Ms. Birgitte Sander Nielsen for skilful work with analysis of the soluble proteins. In addition, the staff of the Department of Surgical Gastroenterology of Hvidovre University Hospital is thanked for valuable support in the collection of intraoperative blood samples. The study was supported by grants from the Kornerup Fund, the Aage and Johanne Louis‐Hansen Fund, the Aase and Ejnar Danielsen Fund, the Walter and O. Kristiane Christensen Fund, the Jacob and Olga Madsen Fund, the Foundation for Improvement of Medical Science and the Danish Cancer Society.