Claudin-18 (CLDN18) is a protein belonging to the claudin family, specifically expressed in stomach epithelial cells where it plays a crucial role in the formation of tight junctions [1]. Tight junctions are essential for maintaining the integrity and selective permeability of epithelial and endothelial barriers by regulating the passage of solutes and ions between cells [2]. CLDN18 has two tissue-specific isoforms, claudin-18a1 found in the lung and claudin-18a2 in the stomach [3]. In the stomach, CLDN18 is highly specific to the tissue and is a key component of tight junctions [4].
Research has shown that CLDN18 is involved in various cancers, including gastric cancer, where it can form fusion genes like CLDN18-ARHGAP [1]. Additionally, CLDN18 has been identified as a potential diagnostic biomarker and therapeutic target in pancreatic cancer [5]. The expression of CLDN18 has been linked to different types of tumors, such as intestinal-type mucinous borderline tumors of the ovary and gallbladder carcinoma [6][2]. Moreover, CLDN18 deficiency has been associated with alveolar barrier dysfunction and impaired alveologenesis in mice, highlighting its importance in lung function [7].
Furthermore, CLDN18 has been studied in the context of tight junction regulation, with research showing its involvement in paracellular proton barriers in the stomach [8]. The expression profiling of CLDN18, along with other markers like Annexin A10 and SOX2, has been used to determine the origin of certain carcinomas [9]. Overall, CLDN18 emerges as a significant protein involved in tight junction formation, cancer development, and tissue-specific functions, making it a promising target for further research and potential therapeutic interventions.
References:
[1] I. Nakayama, E. Shinozaki, S. Sakata, N. Yamamoto, J. Fujisaki, Y. Muramatsuet al., "Enrichment of cldn18‐arhgap fusion gene in gastric cancers in young adults", Cancer Science, vol. 110, no. 4, p. 1352-1363, 2019. https://doi.org/10.1111/cas.13967
[2] J. Espinoza, I. Riquelme, E. Sagredo, L. Rosa, P. García, C. Bizamaet al., "Mucin 5b, carbonic anhydrase 9 and claudin 18 are potential theranostic markers of gallbladder carcinoma", Histopathology, vol. 74, no. 4, p. 597-607, 2019. https://doi.org/10.1111/his.13797
[3] K. Yano, T. Imaeda, & T. Niimi, "Transcriptional activation of the humanclaudin-18gene promoter through two ap-1 motifs in pma-stimulated mkn45 gastric cancer cells", Ajp Gastrointestinal and Liver Physiology, vol. 294, no. 1, p. G336-G343, 2008. https://doi.org/10.1152/ajpgi.00328.2007
[4] I. Coati, G. Lotz, G. Fanelli, S. Brignola, C. Lanza, R. Cappellessoet al., "Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases", British Journal of Cancer, vol. 121, no. 3, p. 257-263, 2019. https://doi.org/10.1038/s41416-019-0508-4
[5] J. Li, Y. Zhang, & D. Hu, "Identification of cldn18 as a potential diagnostic biomarker and therapeutic target for pancreatic cancer based on multiomic analysis",, 2020. https://doi.org/10.21203/rs.3.rs-15518/v1
[6] S. Halimi, D. Maeda, A. Shinozaki‐Ushiku, T. Koso, K. Matsusaka, M. Tanakaet al., "Claudin‐18 overexpression in intestinal‐type mucinous borderline tumour of the ovary", Histopathology, vol. 63, no. 4, p. 534-544, 2013. https://doi.org/10.1111/his.12182
[7] M. LaFemina, K. Sutherland, T. Bentley, L. Gonzales, L. Allen, C. Chapinet al., "Claudin-18 deficiency results in alveolar barrier dysfunction and impaired alveologenesis in mice", American Journal of Respiratory Cell and Molecular Biology, vol. 51, no. 4, p. 550-558, 2014. https://doi.org/10.1165/rcmb.2013-0456oc
[8] A. Tamura, Y. Yamazaki, D. Hayashi, K. Suzuki, K. Sentani, W. Yasuiet al., "Claudin‐based paracellular proton barrier in the stomach", Annals of the New York Academy of Sciences, vol. 1258, no. 1, p. 108-114, 2012. https://doi.org/10.1111/j.1749-6632.2012.06570.x
[9] R. Isidro, I. Abukhiran, C. Dunseth, M. Gosse, R. Humble, D. Pelletieret al., "Strong annexin a10 expression supports a pancreatic primary and combined annexin a10, claudin 18, and sox2 expression supports an esophagogastric origin in carcinomas of unknown primary", The American Journal of Surgical Pathology, vol. 47, no. 4, p. 440-452, 2022. https://doi.org/10.1097/pas.0000000000001994
