Colorectal cancer patients exhibit increased levels of galanin in serum and colon tissues

Abstract

Galanin (GAL) is a 30-amino acid neuropeptide that is expressed in both the central and peripheral nervous system, including the enteric nervous system (ENS). Increased GAL concentrations have been identified in the blood of colorectal cancer (CRC) patients. The aim of the present study was to assess whether sections of the colon wall containing ENS plexuses or CRC tumor are associated with increased GAL concentrations. Blood samples were collected from 68 CRC patients and 39 healthy volunteers. In addition, samples of CRC tumors and colon wall tissue in close proximity to and distant from the neoplastic tissue were obtained from 22 CRC patients. The GAL concentration of sera and tissue homogenates obtained from three sections of the colon wall (mucosa with submucosa, muscularis externa and CRC tumor) was analyzed by ELISA. The localization of GAL was evaluated using immunohistochemistry and morphometry was used to measure the distribution of GAL-immunoreactive (GAL-Ir) myenteric plexuses in the vicinity of cancer invasion and in sections of the colon wall distant from the tumor. The GAL serum concentration of CRC patients was 2.4 times higher than that of the control group. The GAL concentration was highest in the homogenates of neoplastic tissue and mucosa obtained from the control (distant) section of the intestinal wall, followed by that in the mucosa and muscularis externa proximal to the tumor. The lowest GAL concentrations were identified within the muscular layer of the colon wall located distant from the tumor. Strong GAL immunoreactivity was identified in the cancer cells, intestinal epithelium and the submucosal and myenteric plexuses. Morphometric analysis revealed that the GAL-Ir myenteric plexuses in the vicinity of tumor infiltration were significantly smaller in size than those in the intact section of the large intestine. Furthermore, no associations were identified between the clinicopathological characteristics of CRC patients and GAL serum and tissue concentration. The increased GAL serum concentrations observed in CRC patients in comparison to healthy controls may result from GAL secretion by CRC tumors, however, other sources of GAL cannot be excluded. The atrophy of myenteric plexuses within close proximity to the tumor may affect the colon function of CRC patients. In conclusion, investigation into the presence of GAL in the colon wall and serum of CRC patients revealed that serum and tissue GAL levels may present useful potential biomarkers in CRC patients.

Ultrastructural characteristics of myenteric plexus in patients with colorectal cancer

“…They found significant reduction (by approximately 50%) of the area occupied by galanin-immunoreactive neurons in the MPs located in the vicinity of CRC invasion in comparison to distally located plexuses. The authors suggested that neither apoptosis nor necrosis has been involved in the observed phenomena [15,16]. These finding have been confirmed by the results of our ultrastructural study, which showed neither neurons' apoptosis nor necrosis to occur in myenteric plexuses located close to the CRC tumor.…”

“…Our study presents an attempt to explain the observations by Kwiatkowski et al [15] and Kozlowska et al [16] who applied morphometry to measure the area of MPs close to and distant from CRC invasion. They found significant reduction (by approximately 50%) of the area occupied by galanin-immunoreactive neurons in the MPs located in the vicinity of CRC invasion in comparison to distally located plexuses.…”

Co-expression of caspase-3 or caspase-8 with galanin in the human stomach section affected by carcinoma

“…Latest studies showed that ENS may undergo severe decomposition under various pathological conditions. For example, it was reported that MPs in the vicinity of the colorectal cancer (CRC) tissue were significantly smaller and had lower number of neurons per plexus compared to distally located plexuses [ 5 , 6 ]. Similar observations were also reported in the colon wall of patients with diabetes [ 7 ] and severe constipation [ 8 ].…”

“…In the ENS, this neuropeptide is hypothesized to influence the gastrointestinal motility (by inhibition of acetylcholine and substance P release from excitatory motor neurons) as well as secretion (through GAL 1 receptors—GAL-R 1 ) [ 14 ]. Elevated GAL levels in the serum and colon tissues were observed in patients with CRC [ 6 ]. Thus it has been proposed that an increase in number of GAL-immunoreactive (-IR) neurons can be associated with adaptive and neuroprotective possibilities of the enteric neurons that is well-documented in many experimental models of brain and neurons injury [ 15 , 16 ].…”

Changes in the Distribution of Cocaine- and Amphetamine-Regulated Transcript-Containing Neural Structures in the Human Colon Affected by the Neoplastic Process

“…Nerve damage within the large intestine has been observed during inflammatory diseases [ 23 , 24 ], as well as in colon cancer [ 25 ]. Moreover, in the case of the latter disease, the most visible changes concerned the expression of neuronal active substances in the ENS [ 26 , 27 , 28 , 29 ]. Previous studies showed that CART-LI in the enteric neurons may also be subject to such changes.…”