ALCAM/CD166在炎症性疾病中的作用机制及临床意义
Mechanisms and Clinical Significance of ALCAM/CD166 in Inflammatory Diseases
DOI: 10.12677/acm.2026.163808, PDF,   
作者: 田怡柯：重庆医科大学附属第二医院感染病科，感染性疾病分子生物学教育部重点实验室，重庆医科大学病毒性肝炎研究所，重庆；重庆医科大学附属第一医院检验科，重庆；陈 娟*：重庆医科大学附属第二医院感染病科，感染性疾病分子生物学教育部重点实验室，重庆医科大学病毒性肝炎研究所，重庆；曹 炬*：重庆医科大学附属第一医院检验科，重庆
关键词: ALCAM；CD166；炎症；免疫调控；生物标志物；ALCAM； CD166； Inflammation； Immune Regulation； Biomarker
摘要: 活化白细胞黏附分子(ALCAM, CD166)作为免疫球蛋白超家族成员，在免疫调控和炎症反应中发挥关键作用。其可通过介导细胞黏附及调控共刺激信号，参与T细胞活化增殖及免疫细胞向炎症部位的迁移，从而放大炎症反应。ALCAM的胞外结构域可被ADAM17剪切形成可溶性ALCAM (sALCAM)，血液或体液中的sALCAM水平可作为炎症状态的潜在指标。越来越多的研究显示，ALCAM在炎症性疾病中可导致炎症加剧和组织损伤，而阻断或干预其可有效缓解炎症和组织损伤。基于此，本文系统综述了ALCAM在炎症性疾病中的表达特征、分子机制及临床意义，为进一步的研究和潜在干预策略提供参考。
Abstract: Activated leukocyte cell adhesion molecule (ALCAM, CD166), a member of the immunoglobulin superfamily, plays a critical role in immune regulation and inflammatory responses. ALCAM mediates cell adhesion and modulates co-stimulatory signaling. It contributes to T cell activation, proliferation, and the migration of immune cells to sites of inflammation, thereby amplifying inflammatory responses. The extracellular domain of ALCAM can be cleaved by ADAM17 to generate soluble ALCAM (sALCAM), the levels of which in blood or other body fluids can serve as a potential indicator of inflammatory status. Increasing evidence indicates that ALCAM contributes to inflammation exacerbation and tissue damage in inflammatory diseases. Blockade or deficiency of it significantly alleviates inflammation and improves tissue damage, suggesting its potential value in therapeutic intervention. Based on these findings, this review systematically summarizes the expression patterns, molecular mechanisms, and clinical significance of ALCAM in inflammatory diseases, providing a reference for further research and potential therapeutic strategies.
文章引用：田怡柯, 陈娟, 曹炬. ALCAM/CD166在炎症性疾病中的作用机制及临床意义[J]. 临床医学进展, 2026, 16(3): 438-445. https://doi.org/10.12677/acm.2026.163808

参考文献

[1] Yang, Y.M., Ye, L., Ruge, F., Fang, Z., Ji, K., Sanders, A.J., et al. (2023) Activated Leukocyte Cell Adhesion Molecule (ALCAM), a Potential ‘Seed’ and ‘Soil’ Receptor in the Peritoneal Metastasis of Gastrointestinal Cancers. International Journal of Molecular Sciences, 24, Article 876. [Google Scholar] [CrossRef] [PubMed]
[2] Bowen, M.A., Patel, D.D., Li, X., Modrell, B., Malacko, A.R., Wang, W.C., et al. (1995) Cloning, Mapping, and Characterization of Activated Leukocyte-Cell Adhesion Molecule (ALCAM), a CD6 Ligand. The Journal of experimental medicine, 181, 2213-2220. [Google Scholar] [CrossRef] [PubMed]
[3] Arai, F., Ohneda, O., Miyamoto, T., Zhang, X.Q. and Suda, T. (2002) Mesenchymal Stem Cells in Perichondrium Express Activated Leukocyte Cell Adhesion Molecule and Participate in Bone Marrow Formation. The Journal of Experimental Medicine, 195, 1549-1563. [Google Scholar] [CrossRef] [PubMed]
[4] Hansen, A.G., Swart, G.W. and Zijlstra, A. (2011) ALCAM: Basis Sequence: Mouse. AFCS Nat Mol Pages.
[5] Weidle, U.H., Eggle, D., Klostermann, S. and Swart, G.W. (2010) ALCAM/CD166: Cancer-Related Issues. Cancer Genomics Proteomics, 7, 231-243.
[6] Hansen, A.G., Arnold, S.A., Jiang, M., Palmer, T.D., Ketova, T., Merkel, A., et al. (2014) ALCAM/CD166 Is a TGF-β—Responsive Marker and Functional Regulator of Prostate Cancer Metastasis to Bone. Cancer Research, 74, 1404-1415. [Google Scholar] [CrossRef] [PubMed]
[7] Swart, G.W.M., Lunter, P.C., Kilsdonk, J.W.J.V. and Kempen, L.C.L.T.V. (2005) Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166): Signaling at the Divide of Melanoma Cell Clustering and Cell Migration? Cancer and Metastasis Reviews, 24, 223-236. [Google Scholar] [CrossRef] [PubMed]
[8] van Kempen, L.C.L.T., Nelissen, J.M.D.T., Degen, W.G.J., Torensma, R., Weidle, U.H., Bloemers, H.P.J., et al. (2001) Molecular Basis for the Homophilic Activated Leukocyte Cell Adhesion Molecule (ALCAM)-ALCAM Interaction. Journal of Biological Chemistry, 276, 25783-25790. [Google Scholar] [CrossRef] [PubMed]
[9] von Lersner, A., Droesen, L. and Zijlstra, A. (2019) Modulation of Cell Adhesion and Migration through Regulation of the Immunoglobulin Superfamily Member ALCAM/CD166. Clinical & Experimental Metastasis, 36, 87-95. [Google Scholar] [CrossRef] [PubMed]
[10] Swart, G.W.M. (2002) Activated Leukocyte Cell Adhesion Molecule (CD166/ALCAM): Developmental and Mechanistic Aspects of Cell Clustering and Cell Migration. European Journal of Cell Biology, 81, 313-321. [Google Scholar] [CrossRef] [PubMed]
[11] Resnick, D., Pearson, A. and Krieger, M. (1994) The SRCR Superfamily: A Family Reminiscent of the Ig Superfamily. Trends in Biochemical Sciences, 19, 5-8. [Google Scholar] [CrossRef] [PubMed]
[12] Bowen, M.A., Bajorath, J., Siadak, A.W., Modrell, B., Malacko, A.R., Marquardt, H., et al. (1996) The Amino-Terminal Immunoglobulin-Like Domain of Activated Leukocyte Cell Adhesion Molecule Binds Specifically to the Membrane-Proximal Scavenger Receptor Cysteine-Rich Domain of CD6 with a 1:1 Stoichiometry. Journal of Biological Chemistry, 271, 17390-17396. [Google Scholar] [CrossRef] [PubMed]
[13] Zimmerman, A.W., Joosten, B., Torensma, R., Parnes, J.R., van Leeuwen, F.N. and Figdor, C.G. (2006) Long-Term Engagement of CD6 and ALCAM Is Essential for T-Cell Proliferation Induced by Dendritic Cells. Blood, 107, 3212-3220. [Google Scholar] [CrossRef] [PubMed]
[14] Bech-Serra, J.J., Santiago-Josefat, B., Esselens, C., Saftig, P., Baselga, J., Arribas, J., et al. (2006) Proteomic Identification of Desmoglein 2 and Activated Leukocyte Cell Adhesion Molecule as Substrates of ADAM17 and ADAM10 by Difference Gel Electrophoresis. Molecular and Cellular Biology, 26, 5086-5095. [Google Scholar] [CrossRef] [PubMed]
[15] Ikeda, K. and Quertermous, T. (2004) Molecular Isolation and Characterization of a Soluble Isoform of Activated Leukocyte Cell Adhesion Molecule That Modulates Endothelial Cell Function. Journal of Biological Chemistry, 279, 55315-55323. [Google Scholar] [CrossRef] [PubMed]
[16] Rosso, O., Piazza, T., Bongarzone, I., Rossello, A., Mezzanzanica, D., Canevari, S., et al. (2007) The ALCAM Shedding by the Metalloprotease ADAM17/TACE Is Involved in Motility of Ovarian Carcinoma Cells. Molecular Cancer Research, 5, 1246-1253. [Google Scholar] [CrossRef] [PubMed]
[17] Ferragut, F., Vachetta, V.S., Troncoso, M.F., Rabinovich, G.A. and Elola, M.T. (2021) ALCAM/CD166: A Pleiotropic Mediator of Cell Adhesion, Stemness and Cancer Progression. Cytokine & Growth Factor Reviews, 61, 27-37. [Google Scholar] [CrossRef] [PubMed]
[18] Gurrea-Rubio, M., Lin, F., Wicha, M.S., Mao-Draayer, Y. and Fox, D.A. (2025) Ligands of CD6: Roles in the Pathogenesis and Treatment of Cancer. Frontiers in Immunology, 15, Article ID: 1528478. [Google Scholar] [CrossRef] [PubMed]
[19] Kozovska, Z., Gabrisova, V. and Kucerova, L. (2014) Colon Cancer: Cancer Stem Cells Markers, Drug Resistance and Treatment. Biomedicine & Pharmacotherapy, 68, 911-916. [Google Scholar] [CrossRef] [PubMed]
[20] Yang, Y., Sanders, A.J., Dou, Q.P., Jiang, D.G., Li, A.X. and Jiang, W.G. (2021) The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers. Cancers, 13, Article 5187. [Google Scholar] [CrossRef] [PubMed]
[21] Chen, X., Liang, R., Lin, H., Chen, K., Chen, L., Tian, G., et al. (2021) CD166 Promotes Cancer Stem Cell-Like Phenotype via the EGFR/ERK1/2 Pathway in the Nasopharyngeal Carcinoma Cell Line Cne-2r. Life Sciences, 267, Article 118983. [Google Scholar] [CrossRef] [PubMed]
[22] Tachezy, M., Effenberger, K., Zander, H., Minner, S., Gebauer, F., Vashist, Y.K., et al. (2011) ALCAM (CD166) Expression and Serum Levels Are Markers for Poor Survival of Esophageal Cancer Patients. International Journal of Cancer, 131, 396-405. [Google Scholar] [CrossRef] [PubMed]
[23] Li, R., Ren, T., Zeng, J. and Xu, H. (2022) ALCAM Deficiency Alleviates LPS-Induced Acute Lung Injury by Inhibiting Inflammatory Response. Inflammation, 46, 688-699. [Google Scholar] [CrossRef] [PubMed]
[24] Ma, C., Wu, W., Lin, R., Ge, Y., Zhang, C., Sun, S., et al. (2018) Critical Role of CD6highCD4+ T Cells in Driving Th1/th17 Cell Immune Responses and Mucosal Inflammation in IBD. Journal of Crohn’s and Colitis, 13, 510-524. [Google Scholar] [CrossRef] [PubMed]
[25] Semitekolou, M. and Xanthou, G. (2018) Activated Leukocyte Cell Adhesion Molecule: A Novel Regulator of Allergic Inflammation in the Airways. American Journal of Respiratory and Critical Care Medicine, 197, 973-975. [Google Scholar] [CrossRef] [PubMed]
[26] Sulaj, A., Kopf, S., Gröne, E., Gröne, H., Hoffmann, S., Schleicher, E., et al. (2017) ALCAM a Novel Biomarker in Patients with Type 2 Diabetes Mellitus Complicated with Diabetic Nephropathy. Journal of Diabetes and its Complications, 31, 1058-1065. [Google Scholar] [CrossRef] [PubMed]
[27] Ueland, T., Åkerblom, A., Ghukasyan, T., Michelsen, A.E., Becker, R.C., Bertilsson, M., et al. (2020) ALCAM Predicts Future Cardiovascular Death in Acute Coronary Syndromes: Insights from the PLATO Trial. Atherosclerosis, 293, 35-41. [Google Scholar] [CrossRef] [PubMed]
[28] von Bauer, R., Oikonomou, D., Sulaj, A., Mohammed, S., Hotz-Wagenblatt, A., Gröne, H., et al. (2013) CD166/ALCAM Mediates Proinflammatory Effects of S100B in Delayed Type Hypersensitivity. The Journal of Immunology, 191, 369-377. [Google Scholar] [CrossRef] [PubMed]
[29] Kim, M.N., Hong, J.Y., Shim, D.H., Sol, I.S., Kim, Y.S., Lee, J.H., et al. (2018) Activated Leukocyte Cell Adhesion Molecule Stimulates the T-Cell Response in Allergic Asthma. American Journal of Respiratory and Critical Care Medicine, 197, 994-1008. [Google Scholar] [CrossRef] [PubMed]
[30] Zhang, J., Ghosh, J., Mohamad, S.F., Zhang, C., Huang, X., Capitano, M.L., et al. (2019) CD166 Engagement Augments Mouse and Human Hematopoietic Progenitor Function via Activation of Stemness and Cell Cycle Pathways. Stem Cells, 37, 1319-1330. [Google Scholar] [CrossRef] [PubMed]
[31] Baek, S.M., Kim, M.N., Kim, E.G., Lee, Y.J., Park, C.H., Kim, M.J., et al. (2024) Activated Leukocyte Cell Adhesion Molecule Regulates the Expression of Interleukin-33 in RSV Induced Airway Inflammation by Regulating MAPK Signaling Pathways. Lung, 202, 127-137. [Google Scholar] [CrossRef] [PubMed]
[32] Oh, M.S., Hong, J.Y., Kim, M.N., Kwak, E.J., Kim, S.Y., Kim, E.G., et al. (2019) Activated Leukocyte Cell Adhesion Molecule Modulates Th2 Immune Response in Atopic Dermatitis. Allergy, Asthma & Immunology Research, 11, 677-690. [Google Scholar] [CrossRef] [PubMed]
[33] Kim, Y.S., Kim, M.N., Lee, K.E., Hong, J.Y., Oh, M.S., Kim, S.Y., et al. (2018) Activated Leucocyte Cell Adhesion Molecule (ALCAM/CD166) Regulates T Cell Responses in a Murine Model of Food Allergy. Clinical and Experimental Immunology, 192, 151-164. [Google Scholar] [CrossRef] [PubMed]
[34] Chalmers, S.A., Ayilam Ramachandran, R., Garcia, S.J., Der, E., Herlitz, L., Ampudia, J., et al. (2022) The CD6/ALCAM Pathway Promotes Lupus Nephritis via T Cell-Mediated Responses. Journal of Clinical Investigation, 132, e147334. [Google Scholar] [CrossRef] [PubMed]
[35] Kenney, H.M., Rangel-Moreno, J., Peng, Y., Chen, K.L., Bruno, J., Embong, A., et al. (2023) Multi-Omics Analysis Identifies IgG2b Class-Switching with ALCAM-CD6 Co-Stimulation in Joint-Draining Lymph Nodes during Advanced Inflammatory-Erosive Arthritis. Frontiers in Immunology, 14, Article ID: 1237498. [Google Scholar] [CrossRef] [PubMed]
[36] Willrodt, A., Salabarria, A., Schineis, P., Ignatova, D., Hunter, M.C., Vranova, M., et al. (2019) ALCAM Mediates DC Migration through Afferent Lymphatics and Promotes Allospecific Immune Reactions. Frontiers in Immunology, 10, Article ID: 759. [Google Scholar] [CrossRef] [PubMed]
[37] Cayrol, R., Wosik, K., Berard, J.L., Dodelet-Devillers, A., Ifergan, I., Kebir, H., et al. (2007) Activated Leukocyte Cell Adhesion Molecule Promotes Leukocyte Trafficking into the Central Nervous System. Nature Immunology, 9, 137-145. [Google Scholar] [CrossRef] [PubMed]
[38] Wagner, M., Bilinska, M., Pokryszko-Dragan, A., Sobczynski, M., Cyrul, M., Kusnierczyk, P., et al. (2014) ALCAM and CD6—Multiple Sclerosis Risk Factors. Journal of Neuroimmunology, 276, 98-103. [Google Scholar] [CrossRef] [PubMed]
[39] Ibáñez, A., Sarrias, M., Farnós, M., Gimferrer, I., Serra-Pagès, C., Vives, J., et al. (2006) Mitogen-Activated Protein Kinase Pathway Activation by the CD6 Lymphocyte Surface Receptor. The Journal of Immunology, 177, 1152-1159. [Google Scholar] [CrossRef] [PubMed]

为你推荐