Gallegos, Nicholas Charles; (1993) Tumour invasion and metastasis in colorectal cancer: An immunohistochemical study into the role of matrix metalloproteinase enzymes, TIMP-1, and circulating tumour cells. Masters thesis (M.Surg), UCL (University College London).

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Abstract

The enzymatic degradation of surrounding connective tissue followed by the intravasation and circulation of tumour cells represent initial steps in metastasis. In a study of colorectal cancer the technique of immunohistochemistry was used to examine the role played by the matrix metalloproteinase enzymes interstitial collagenase, gelatinase and stromelysin and their inhibitor TIMP-1 in tumour invasion, and to detect and quantify blood borne tumour cells in mesenteric and peripheral vein blood samples. A role for stromelysin and Mr 72,000 gelatinase in tumour invasion was supported by immunolocalizing both enzymes to the connective tissue matrix, fibroblast-like cells or mononuclear cells within biopsies of tumour tissue and not to those of normal mucosa. There was no evidence that the tumour cells were responsible for the synthesis of these enzymes. By contrast interstitial collagenase was not identified. TIMP-1 predominantly immunolocalized to endothelial cells and was identified most frequently at the tumour/mucosal interface implying a possible role in modulating tumour invasion. Additionally evidence from immunostained Western blots prepared from the polyacrylamide gel electrophoresis of colonic mucus suggested that TIMP-1 was present in colonic mucus. Circulating tumour cells were identified in 4 of 14 patients using the anti-cytokeratin antibody 8.13. Cells were present in concentrations ranging from 40 cells ml-1 to 954 cells ml-1. These studies provide new information on the mechanism of tumour invasion and form the basis for further investigations aimed at correlating matrix metalloproteinase and TIMP-1 expression with the biological behaviour of colorectal tumours. The ability to detect and quantify circulating tumour cells with increased reliability also provides a foundation for a further study into the characteristics of these cells.

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