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Mucin (MUC) is a type of high molecular weight glycoprotein secreted by tissue mucosa and covered on the surface of mucosal epithelium. At present, more than 20 types of MUC have been identified, including two major types: secretory and membrane-bound. Secretory MUC mainly exists and is expressed in the form of mucus on the mucosal surface, and membrane-bound MUC mainly exists and is expressed in the form of transmembrane on the surface of epithelial cells. Under normal circumstances, MUC is secreted and covers the mucosal surface. It not only participates in various physiological activities of the body, but also plays a very important role in cell protection, lubrication and cell adhesion. Studies have shown that MUC is crucial to the occurrence and development of tumors, and participates in physiological activities such as signal transduction and immune regulation. The occurrence and development of gastric cancer, liver cancer, lung cancer, pancreatic cancer and breast cancer are closely related to the abnormal expression of MUC. MUC can be used as a specific tumor marker. Therefore, detecting the expression level of MUC in tumor tissue is of great significance for diagnosing malignant tumors, judging prognosis and monitoring recurrence. Mucin 1 (MUC1, CA 27-29) plays an important role in many tumors and is the most intensively studied type of MUC to date. In 2009, the National Cancer Institute of the United States listed MUC1 as the second largest targeted therapeutic antigen for tumor vaccine development among 75 tumor-associated antigens. In 2017, the number of clinical trials related to MUC1 also began to increase sharply, indicating that MUC1 as a tumor treatment target has been a research hotspot in recent years.
Figure 1. Structure of mucin 1. (Sources: Okarvi SM, et al. 2019)
MUC1 was first discovered in human milk and is shed from the epithelial cells that secrete milk. It is the earliest type discovered in the MUC family. The MUC1 gene is located on chromosome 1q21 and was first cloned from a complementary DNA (cDNA) library constructed from breast cancer and other cell lines. It contains 7 exons, of which the second exon contains a variable number of tandem repeats (VNTRs). The MUC1 protein contains two subunits, namely the amino-terminal region (MUC1-N) and the carboxyl-terminal region (MUC1-C) of MUC1. MUC1-N contains 20 to 120 variable numbers of VNTRs, which constitute the core component of MUC, and each VNTR contains 20 amino acids that can be highly O-glycosylated. In a normal physiological environment, MUC1 can be expressed in the epithelium of various tissues and organs, and can protect and lubricate epithelial cells in the respiratory tract, gastrointestinal tract, and reproductive tract. MUC1 is also a type of protein that can participate in signal cascade reactions, affecting various aspects of cell biological behavior through the interaction between ligands and membrane receptors. MUC expressed by epithelial cells participates in many biological processes, among which the immunomodulatory effect of MUC is related to various tumors. Abnormal glycosylation of MUC can cause the formation of tumor cell-specific antigen epitopes, which can be recognized by the immune system as tumor-associated antigens (TAA), and is an important target in tumor immunotherapy. Similarly, MUC1 also shows characteristics such as upregulated expression, abnormal glycosylation, and non-polar distribution in tumor cells, and plays an important role in the occurrence and development of tumors by regulating tumor cell proliferation, epithelial-mesenchymal transition, and epigenetics. Due to the abnormal increase in the expression of MUC1 in tumor cells and the disappearance of cell polarity, MUC1 is distributed throughout the cell surface and can be hydrolyzed into small fragments by various enzymes and fall off from MUC1-C, so that MUC1 can be detected in the blood. MUC1 fragments shed into the blood can also affect tumor immunotherapy, such as interfering with natural killer cell-mediated tumor cell lysis, inhibiting T cell proliferation, etc., and can bind to antibodies injected into the body, thereby reducing the number of unbound antibodies. MUC1 is also related to biological processes such as cell proliferation, invasion, metastasis and angiogenesis. For example, MUC1 can interact with cell adhesion molecule-1, E-selectin and galectin-3 to activate mechanisms such as cell migration and invasion; the interaction between MUC1 and hypoxia-inducible factor-1α can also upregulate the expression of vascular endothelial growth factor and promote tumor angiogenesis. Therefore, inhibiting the activity of MUC1 may become an effective way to treat tumors. The high expression of MUC1 in tumors makes it a potential tumor biomarker and therapeutic target, and it is used in the diagnosis and biological treatment of various tumors.
Tumor biomarkers are commonly used clinically to assist in evaluating treatment effects and prognosis. One of the more widely used subtypes of MUC1 is carbohydrate antigen 153 (CA153), which plays an important role in the auxiliary diagnosis of breast cancer. Studies have reported that MUC1 is a biomarker for early detection of gastric cancer, and its expression level is significantly related to the tumor grade of colorectal cancer, so it can be used as a biomarker to evaluate patient prognosis. MUC1 can be detected in pancreatic cancer at different stages of development and can be used to predict the occurrence and development of pancreatic cancer. In recent years, in order to further improve the accuracy and sensitivity of MUC1 detection, new sensors have emerged that can efficiently detect and quantify MUC1, such as MUC1 aptamer-coupled PtAu nanoparticles, which are developed from nanomaterials with unique physical and chemical properties. Recently, it can be used to accurately identify MUC1 on the surface of tumor cells; new radiolabeled targeting molecules with biological properties have also been used to target tumor-specific MUC1 to diagnose and treat tumors. In addition, MUC1 is closely related to immune checkpoint genes, neoantigens It is significantly correlated with certain prognostic indicators of immunotherapy, such as tumor mutation load and microsatellite instability, indicating that it can also be used as a target for immunotherapy and a biomarker for prognosis prediction.
Anti-CA 27-29 monoclonal antibody
CA 27-29 mAb
CA27-29 antibody
Cancer Antigen 27-29 monoclonal antibody
MUC1 monoclonal antibody
References
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