Local up-regulation of neuropeptide receptors in host blood vessels around human colorectal cancers (original) (raw)

Background & Aims: Neuropeptide receptors, exlarly of the vasculature in the tumor bed, 8 remains expressed at high density by neoplastic cells, can be tremely scarce. instrumental for diagnosis and therapy. However, little Somatostatin receptors (SS-Rs) are abundantly exis known about neuropeptides and neuropeptide receppressed by several human tumors, including neuroendotors in the tumor bed. The aim of this study was to crine gut tumors; others, such as colorectal carcinomas, study the expression of two neuropeptide receptors in rarely display SS-Rs. 9 Substance P receptors (SP-Rs) also peritumoral blood vessels. Methods: Somatostatin and are expressed by various human cancers, such as glial substance P receptors were measured using in vitro tumors or medullary thyroid carcinomas, whereas coloreceptor autoradiography in well-defined submucosal rectal cancers rarely express SP-Rs. 10 In addition, both and subserosal vessels located in the immediate sur-SS-Rs and SP-Rs can be expressed by vessels, either in roundings of human colorectal carcinomas or in normal normal tissues or, at higher density, in several pathologicolon taken at increasing distances from the tumor. cal conditions such as rheumatoid arthritis or inflamma-Results: Both receptors were 3-5-fold overexpressed in the host veins within a 2-cm-wide area surrounding tory bowel disease. 11-14 SS-Rs are expressed by veins, SPhuman primary colorectal carcinomas compared with Rs are expressed by veins and arteries, and both mediate veins located at 5-10-cm distance in normal gut tisthe vasoregulatory functions of the peptides. 15,16 Theresue. The expression of peritumoral vascular somatofore, SS-Rs and SP-Rs are optimal candidates for the statin receptor and substance P receptor appears indeevaluation of altered biochemical characteristics in the pendent of receptor expression in the tumor, of tumor vessels of the peritumoral area. stage, and of the grade of local inflammation. Conclu-Using receptor autoradiography for SS-Rs 11 and SPsions: These biochemical alterations of veins in the Rs, 10,14 we have evaluated the tumoral and vascular recepimmediate vicinity of tumors represent a novel tumortor status in large resected samples of human colorectal related site of expression for the two receptors and carcinomas including at least 10 cm of adjacent (proximay point to a new biological principle of host-tumor mal) colonic tissue. Colorectal cancer was chosen because interaction. Thus, vascular regulatory mechanisms in (1) preliminary studies showed expression of SS-Rs in the tumor bed may be important for tumor development and metastasis and may be used as a target for tumor peritumoral vessels 8 and (2) the large amount of normal, therapy.