Expression of the endogenous, nicotinic acetylcholine receptor ligand, SLURP‐1, in human colon cancer

Abstract

1. Secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein-1 (SLURP-1) is a recently discovered endogenous ligand at the alpha7 subunit of the nicotinic acetylcholine receptors. Previous reports have shown that SLURP-1 is expressed in normal human keratinocytes seemingly with a pro-apoptotic function. Conversely, such expression was markedly attenuated in transformed cells and it was suggested that the molecule could convey protection against malignant transformation. 2. In this study, we demonstrated the mRNA expression (by RT-PCR) and protein expression (by Western blotting and immunocytochemistry) of SLURP-1 in the human colon cancer cell line, HT-29. 3. Furthermore, we demonstrated the expression of SLURP-1 (by immunohistochemistry) in tumour cells of human colon cancer tissue, and, to a greater extent, in immune and smooth muscle cells of adjacent, macroscopically tumour-free colon tissue. 4. The current findings suggest that SLURP-1 participates in the regulation of gut immune functions and motility, as well as possibly playing a role in colon carcinogenesis/cancer progression.

Positive and negative modulation of nicotinic receptors

“…Thus, SLURPs as well as ACh can regulate lymphocyte function via AChR-mediated pathways (Moriwaki et al, 2007). Additional evidence indicates that SLURP-1 participates in the regulation of gut immune functions and motility (Pettersson et al, 2008). Mutations in the gene-encoding SLURP-1 produces the Mal de Meleda, a rare autosomal recessive palmoplantar keratoderma characterized by an inflammatory, malodorous, sharply demarcated hyperkeratosis of the palms and soles (Chimenti et al, 2003;Favre et al, 2007;reviewed in Grando, 2008).…”

The Non-Neuronal Cholinergic System in Health and Disease

“…Like in other cancer cells, stimulation of α 7 -nAChR by ACh or nicotine is able to induce cell proliferation and to inhibit apoptosis of colon cancer cells [99]. α 7 -nAChR is negatively regulated by SLURP-1 that is also present in colon cancer cells as well as in the immune cells of the lamina propria and smooth muscle tissue of the colon [98,100]. …”

Anti-Inflammatory Effects of the Nicotinergic Peptides SLURP-1 and SLURP-2 on Human Intestinal Epithelial Cells and Immunocytes

“…These findings suggest that SLURPs may become prototype drugs for the treatment of IBD, because they mimic the inhibitory effect of nicotine and some noncanonical nAChR ligands on gut inflammation. Clinical use of rSLURPs should avoid nicotine-like toxicity, such as off-target and nonreceptor intracellular effects, because SLURPs are the physiological substances produced at low levels by IEC [25] and immunocytes [60] that alter cell functions by acting at nAChRs [46, 47]. Notably, quercetin—a flavonoid that exhibits its nicotinergic activity through α 3, α 7, and α 9 nAChRs [61–64]—produces an anti-inflammatory effect and ameliorates experimental IBD [65, 66].…”