Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma.

Abstract

Abstract:The aim of this study was to investigate the arrangement and chemical coding of enteric nerve structures in the human large intestine affected by cancer. Tissue samples comprising all layers of the intestinal wall were collected during surgery form both morphologically unchanged and pathologically altered segments of the intestine (n=15), and fixed by immersion in buffered paraformaldehyde solution. The cryostat sections were processed for double-labelling immunofluorescence to study the distribution of the intramural nerve structures (visualized with antibodies against protein gene-product 9.5) and their chemical coding using antibodies against somatostatin (SOM), substance P (SP) and calcitonin gene-related peptide (CGRP). The microscopic observations revealed distinct morphological differences in the enteric nerve system structure between the region adjacent to the cancer invaded area and the intact part of the intestine. In general, infiltration of the cancer tissue resulted in the gradual (depending on the grade of invasion) first decomposition and reduction to final partial or complete destruction and absence of the neuronal elements. A comparative analysis of immunohistochemically labeled sections (from the unchanged and pathologically altered areas) revealed a statistically significant decrease in the number of CGRP-positive neurons and nerve fibres in both submucous and myenteric plexuses in the transitional zone between morphologically unchanged and cancer-invaded areas. In this zone, a decrease was also observed in the density of SP-positive nerve fibres in all intramural plexuses. Conversely, the investigations demonstrated statistically insignificant differences in number of SP-and SOM-positive neurons and a similar density of SOM-positive nerve fibres in the plexuses of the intact and pathologically changed areas. The differentiation between the potential adaptive changes in ENS or destruction of its elements by cancer invasion should be a subject of further investigations.

Substance P as a neuronal factor in the enteric nervous system of the porcine descending colon in physiological conditions and during selected pathogenic processes

“…The obtained results show that SP-positive neuronal structures are present in all parts of the wall of the porcine descending colon with the exception of the outer muscular layer. SP-like immunoreactivity was observed within neurons and intraganglionic nerve fibers in all kinds of enteric plexuses as well as within nerves in the circular muscular layer and mucosa, what is in accordance with previous studies in various species, including humans [18][19][20][21][22][23][24][25]41,42].…”

“…Till now SP-like immunoreactivity has been observed in various fragments of the GI tract of numerous mammals both in enteric neurons within all types of intramural plexuses, as well as in nerve processes that innervate intestinal muscles and submucosal and mucosal layers [18][19][20][21][22][23][24][25]. SP in the GI tract can play multiple roles according to the species, fragment of the GI tract and type of stimulated receptor .…”

Neuropeptide Levels as well as Neprilysin Activity Decrease in Renal Cell Carcinoma

“…CGRP, widely expressed in central and peripheral nervous systems, [12] also exerts potent anti-inflammatory effects [13] which may decrease cancer formation [14]. In accordance loss of CGRP expression in human colon cancer was reported [15]. SP is found in both neuronal and extraneuronal cells [16] and we recently demosntrated that SP through neuroimmune modulation decreases breast cancer metastasis and enhances the therapeutic effects of radiotherapy [17].…”

The Influence of Low Doses of Zearalenone and T-2 Toxin on Calcitonin Gene Related Peptide-Like Immunoreactive (CGRP-LI) Neurons in the ENS of the Porcine Descending Colon

“…Moreover, significant interspecies differences in the distribution of enteric neurons immunoreactive to CGRP have been established [32,33,34], which can suggest that exact roles of this peptide are different in various animal species. In contrast, the knowledge concerning the distribution of CGRP in the colonic ENS is relatively scarce and essentially limited to humans and rats [35,36]. It should be pointed out that some similarities between humans [16,33,37] and pigs (this study) have been observed.…”