https://doi.org/10.4081/ejh.2024.3990
The role of galanin in the progression and prognosis of colorectal cancer: the unfinished story
Submitted: 14 February 2024
Accepted: 27 February 2024
Published: 6 March 2024
Accepted: 27 February 2024
Abstract Views: 429
PDF: 237
HTML: 4
HTML: 4
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
The paper presents a summary of immunohistochemical (IHC) and biochemical investigations on the presence of galanin (Gal), one of the neuropeptides abundant in the enteric nervous systems, and three types of its receptors (GalR1-3) in colorectal cancer (CRC) tissue and non-involved colon wall and their associations with clinical-pathological data of the CRC patients. We were the first to morphologically demonstrate the presence of endogenous Gal in CRC sections and measure its content in homogenates of tumor tissue and dissected compartments of unchanged colon wall. The prominent atrophy of myenteric plexuses displaying Gal immunoreactivity (Gal-Ir) located close to the tumor invasion was found to be accompanied by higher Gal content in the tumor-adjacent muscularis externa than in tumor-distant tissue. In further studies for the first time, we demonstrated by the IHC technique the presence of the GalR1-3 receptors in the CRC tumors and the colon mucosa and found that higher GalR3-Ir in the tumor tissue correlated with longer overall survival of CRC patients. Furthermore, we discovered that lower GalR1 expression in submucosal plexuses located near the tumor correlated with a better prognosis in patients with CRC. These findings suggest that GalR1 could be considered as a novel therapeutic target in CRC. In conclusion, our morphological investigations provided novel data documenting the involvement of Gal and its receptors in the progression of CRC and showed the usefulness of the IHC technique for the prognosis of CRC patients.
Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 2012;9:286-94.
DOI: https://doi.org/10.1038/nrgastro.2012.32
Sharkey KA, Mawe GM. The enteric nervous system. Physiol Rev 2023;103:1487-564.
DOI: https://doi.org/10.1152/physrev.00018.2022
Rademakers G, Vaes N, Schonkeren S, Koch A, Sharkey KA, Melotte V. The role of enteric neurons in the development and progression of colorectal cancer. Biochim Biophys Acta Rev Cancer 2017;1868:420-34.
DOI: https://doi.org/10.1016/j.bbcan.2017.08.003
Schneider S, Wright CM, Heuckeroth RO. Unexpected roles for the second brain: enteric nervous system as master regulator of bowel function. Annu Rev Physiol 2019;81:235-59.
DOI: https://doi.org/10.1146/annurev-physiol-021317-121515
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.
DOI: https://doi.org/10.3322/caac.21660
Godlewski J, Kmiec Z. Colorectal cancer invasion and atrophy of the enteric nervous system: potential feedback and impact on cancer prognosis. Int J Mol Sci 2020;21:3391.
DOI: https://doi.org/10.3390/ijms21093391
Wang H, Huo R, He K, Cheng L, Zhang S, Yu M, et al. Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance. Cell Oncol (Dordr) 2024;47:1-17.
DOI: https://doi.org/10.1007/s13402-023-00857-y
Godlewski J, Lakomy IM. Changes in vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide and neuropeptide Y-ergic structures of the enteric nervous system in the carcinoma of the human large intestine. Folia Histochem Cytobiol 2010;48:208-16.
DOI: https://doi.org/10.2478/v10042-010-0052-9
Kozlowska A, Kwiatkowski P, Oponowicz A, Majewski M, Kmiec Z, Godlewski J. Myenteric plexuses atrophy in the vicinity of colorectal cancer tissue is not caused by apoptosis or necrosis. Folia Histochem Cytobiol 2016;54:99-107.
DOI: https://doi.org/10.5603/FHC.a2016.0012
Godlewski J, Kaleczyc J. Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma. Folia Histochem Cytobiol 2010;48:475-83.
DOI: https://doi.org/10.2478/v10042-010-0079-y
Godlewski J, Pidsudko Z. Characteristic of galaninergic components of the enteric nervous system in the cancer invasion of human large intestine. Ann Anat 2012;194:368-72.
DOI: https://doi.org/10.1016/j.aanat.2011.11.009
Brzozowska M, Calka J. Review: Occurrence and distribution of galanin in the physiological and inflammatory states in the mammalian gastrointestinal tract. Front Immunol 2021;22:602070.
DOI: https://doi.org/10.3389/fimmu.2020.602070
Sanchez ML, Covenas R. The galaninergic system: A target for cancer treatment. Cancers 2022;14:3755.
DOI: https://doi.org/10.3390/cancers14153755
Rauch I, Kofler B. The galanin system in cancer. Exp Suppl 2010;102:223-41.
DOI: https://doi.org/10.1007/978-3-0346-0228-0_16
Stevenson L, Allen WL, Turkington R, Jithesh PV, Proutski I, Stewart G, et al. Identification of galanin and its receptor GalR1 as novel determinants of resistance to chemotherapy and potential biomarkers in colorectal cancer. Clin Cancer Res 2012;18:5412-26.
DOI: https://doi.org/10.1158/1078-0432.CCR-12-1780
Nagayoshi K, Ueki T, Tashiro K, Mizuuchi Y, Manabe T, Araki H, et al. Galanin plays an important role in cancer invasiveness and is associated with poor prognosis in stage II colorectal cancer. Oncol Rep 2015;33:539-46.
DOI: https://doi.org/10.3892/or.2014.3660
Hoyle CH, Burnstock G. Galanin-like immunoreactivity in enteric neurons of the human colon. J Anat 1989;166:23-33.
Burleigh DE, Furness JB. Distribution and actions of galanin and vasoactive intestinal peptide in the human colon. Neuropeptides 1990;16:77-82.
DOI: https://doi.org/10.1016/0143-4179(90)90115-F
Kwiatkowski P, Godlewski J, Kiezun J, Krazinski BE, Kmiec Z. Colorectal cancer patients exhibit increased levels of galanin in serum and colon tissues. Oncol Lett 2016;12:3323-9.
DOI: https://doi.org/10.3892/ol.2016.5037
Kiezun J, Godlewski J, Krazinski BE, Kozielec Z, Kmiec Z. Galanin receptors (GalR1, GalR2, and GalR3) expression in colorectal cancer tissue and correlations to the overall survival and poor prognosis of CRC patients. Int J Mol Sci 2022;23:3735.
DOI: https://doi.org/10.3390/ijms23073735
Kiezun J, Kiezun M, Krazinski BE, Paukszto L, Koprowicz-Wielguszewska A, Kmiec Z, et al. Galanin receptors (GALR1, GALR2, and GALR3) immunoexpression in enteric plexuses of colorectal cancer patients: correlation with the clinico-pathological parameters. Biomolecules 2022;12:1769.
DOI: https://doi.org/10.3390/biom12121769
Kim KY, Kee MK, Chong SA, Nam MJ. Galanin is up-regulated in colon adenocarcinoma. Cancer Epidemiol. Biomark Prev 2007;16:2373-8.
DOI: https://doi.org/10.1158/1055-9965.EPI-06-0740
Talaat IM, Yakout NM, Soliman ASA, Venkatachalam T, Vinod A, Eldohaji L, et al. Evaluation of galanin expression in colorectal cancer: an immunohistochemical and transcriptomic study. Front Oncol 2022;12:877147.
DOI: https://doi.org/10.3389/fonc.2022.877147
Lang R, Gundlach AL, Holmes FE, Hobson SA, Wynick D, Hoekfelt T, et al. Physiology, signaling, and pharmacology of galanin peptides and receptors: three decades of emerging diversity. Pharmacol Rev 2015;67:118-75.
DOI: https://doi.org/10.1124/pr.112.006536
Brunner SM, Reichmann F, Leitner J, Wölfl S, Bereswill S, Farzi A, et al. Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model. Sci Rep 2021;11:564.
DOI: https://doi.org/10.1038/s41598-020-79456-y
Sipkova J, Kramarikova I, Hynie S, Klenerova V. The galanin and galanin receptor subtypes, its regulatory role in the biological and pathological functions. Physiol Res 2017;66:729-40.
DOI: https://doi.org/10.33549/physiolres.933576
Kolakowski LF Jr, O’Neill GP, Howard AD, Broussard SR, Sullivan KA, Feighner SD, et al. Molecular characterization and expression of cloned human galanin receptors GALR2 and GALR3. J Neurochem 1998;71:2239-51.
DOI: https://doi.org/10.1046/j.1471-4159.1998.71062239.x
Smith KE, Walker MW, Artymyshyn R, Bard J, Borowsky B, Tamm JA, et al. Cloned human and rat galanin GALR3 receptors. Pharmacology and activation of G-protein inwardly rectifying K+ channels. J Biol Chem 1998;273:23321-6.
DOI: https://doi.org/10.1074/jbc.273.36.23321
Benya RV, Marrero JA, Ostrovskiy DA, Koutsouris A, Hecht G. Human colonic epithelial cells express galanin-1 receptors, which when activated cause Cl-secretion. Am J Physiol 1999;276:64-72.
DOI: https://doi.org/10.1152/ajpgi.1999.276.1.G64
Kanazawa T, Misawa K, Misawa Y, Maruta M, Uehara T, Kawada K, et al. Galanin receptor 2 utilizes distinct signaling pathways to suppress cell proliferation and induce apoptosis in HNSCC. Mol Med Rep 2014;10:1289-94.
DOI: https://doi.org/10.3892/mmr.2014.2362
Yoon D, Bae K, Lee MK, Kim JH, Yoon KA. Galanin is an epigenetically silenced tumor suppressor gene in gastric cancer cells. PLoS ONE 2018;13:e0193275.
DOI: https://doi.org/10.1371/journal.pone.0193275
Mei Z, Yang Y, Li Y, Yang F, Li J, Xing N, et al. Galanin suppresses proliferation of human U251 and T98G glioma cells via its subtype 1 receptor. Biol Chem 2017;398:1127-39.
DOI: https://doi.org/10.1515/hsz-2016-0320
Namsolleck P, Kofler B, Moll GN. Galanin 2 receptor: a novel target for a subset of pancreatic ductal adenocarcinoma. Int J Mol Sci 2023;24:10193.
DOI: https://doi.org/10.3390/ijms241210193
El-Salhy M, Starefeldt A. Direct effects of octreotide, galanin and serotonin on human colon cancer cells. Oncol Rep 2003;10:1723-8.
DOI: https://doi.org/10.3892/or.10.6.1723
How to Cite
Kmiec, Z., Kieżun, J., Krazinski, B. E., Kwiatkowski, P., & Godlewski, J. (2024). The role of galanin in the progression and prognosis of colorectal cancer: the unfinished story. European Journal of Histochemistry, 68(1). https://doi.org/10.4081/ejh.2024.3990
Copyright (c) 2024 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- X.C. Xu, X. Abuduhadeer, W.B. Zhang, T. Li, H. Gao, Y.H. Wang, Knockdown of RAGE inhibits growth and invasion of gastric cancer cells , European Journal of Histochemistry: Vol. 57 No. 4 (2013)
- Y. Zhang, W.Y. Ye, J.Q. Wang, S.J. Wang, P. Ji, G.Y. Zhou, G.P. Zhao, H.L. Ge, Y. Wang, dCTP pyrophosphohydrase exhibits nucleic accumulation in multiple carcinomas , European Journal of Histochemistry: Vol. 57 No. 3 (2013)
- Yiming Zhang, Wanqiong Zheng, Liang Zhang, Yechun Gu, Lihe Zhu, Yingpeng Huang, LncRNA FBXO18-AS promotes gastric cancer progression by TGF-β1/Smad signaling , European Journal of Histochemistry: Vol. 67 No. 2 (2023)
- Xiangjun Lu, Jian Shen, Siyuan Huang, Dongdong Liu, Haitao Wang, Tumor cells-derived exosomal PD-L1 promotes the growth and invasion of lung cancer cells in vitro via mediating macrophages M2 polarization , European Journal of Histochemistry: Vol. 67 No. 3 (2023)
- Xuanjin Zhu, Weilu Jia, Yong Yan, Yong Huang, Bailin Wang, NOP14 regulates the growth, migration, and invasion of colorectal cancer cells by modulating the NRIP1/GSK-3β/β-catenin signaling pathway , European Journal of Histochemistry: Vol. 65 No. 3 (2021)
- A. Porzionato, M. Rucinski, V. Macchi, G. Sarasin, L.K. Malendowicz, R. De Caro, ECRG4 expression in normal rat tissues: expression study and literature review , European Journal of Histochemistry: Vol. 59 No. 2 (2015)
- Xin Kong, Qi Wang, Jie Li, Ming Li, Fusheng Deng, Chuanying Li, Mammaglobin, GATA-binding protein 3 (GATA3), and epithelial growth factor receptor (EGFR) expression in different breast cancer subtypes and their clinical significance , European Journal of Histochemistry: Vol. 66 No. 2 (2022)
- C. Fede, G. Albertin, L. Petrelli, M.M. Sfriso, C. Biz, R. De Caro, C. Stecco, Expression of the endocannabinoid receptors in human fascial tissue , European Journal of Histochemistry: Vol. 60 No. 2 (2016)
- Ying Wang, Shifa Yuan, Jing Ma, Hong Liu, Lizhen Huang, Fengzhen Zhang, Substance P is overexpressed in cervical squamous cell carcinoma and promoted proliferation and invasion of cervical cancer cells in vitro , European Journal of Histochemistry: Vol. 67 No. 3 (2023)
- Huiwen Li, Bo Huang, miR-19a targeting CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells , European Journal of Histochemistry: Vol. 66 No. 1 (2022)
You may also start an advanced similarity search for this article.
