Chamary, Vincent Louis; (2001) The innervation and ultrastructure of blood vessels supplying benign and malignant colorectal tumours. Doctoral thesis (M.D), UCL (University College London).

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Abstract

The regulation of vascular tone in vessels supplying colorectal tumours has important therapeutic implications. This study of the blood supply to benign and malignant colorectal tumours focuses on the neural and smooth muscle elements that control vascular calibre. Particular emphasis was placed on the study of submucosal arterioles because of their crucial role in supplying colorectal tumours. They are the feeder vessels to the tumours and are the last vessels of resistance in the mesenteric circulation of the colon. Innervation was studied by means of markers of neurotransmitter and vasoactive substances: neuropeptide Y (NPY) , tyrosine hydroxylase (TH) , vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and the general neuronal marker protein gene product 9.5 (PGP 9.5) . The ultrastructure of blood vessels was determined by electron microscopy. The study confirmed the absence of perivascular nerves in colorectal cancer and showed for the first time a decrease in perivascular innervation in the submucosa adjacent to cancers (p<0.002 for TH and NPY and p<0.015 for VIP). Extrinsic nerve loss appeared greater with cancer of advanced Dukes' stages. Perivascular nerve immunoreactivity around arterioles supplying benign tumours differed from controls. There was a decrease in sympathetic neural immunoreactivity (TH, NPY) and an increase in parasympathetic (VIP) and sensory neural immunoreactivity (CGRP) in the submucosa of polyps compared to controls. SP immunoreactivity did not differ significantly from controls. Whereas at electron microscopy smooth muscle cells in blood vessels of normal mucosa and submucosa showed a contractile phenotype, in cancers the vascular smooth muscles were mainly of a secretory phenotype. In polyps, vascular smooth muscles showed a change towards a secretory phenotype. Benign and malignant colorectal tumours appear to induce changes in the innervation and the expression of smooth muscle phenotypes in blood vessels within and adjacent to the tumours. Perivascular nerve changes may result from release of tumour factors from the tumour cells. The differential expression of neurotransmitters and cell phenotypes in colorectal tumours could be of value as markers of disease and as pointers to targets for therapy.

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