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MUC16, also known as CA125, is a high molecular weight glycoprotein expressed on the surface of various epithelial cells, which plays a major role in protecting and repairing the epithelium. The ovarian tumor cell surface-associated antigen MUC16 is a glycoprotein antigen recognized by the murine monoclonal antibody OC125 produced by the ovarian epithelial cancer cell line OVCA433.
Biological Characteristics of MUC16
MUC16 consists of an N-terminal domain, a C-terminal domain, and tandem repeats. The C-terminal domain contains a transmembrane domain as well as an intracellular tail region with an intracellular domain containing 31 amino acids and a potential phosphorylation site. It undergoes phosphorylation under specific conditions, which may be related to the involvement of MUC16 in related signaling pathways. In addition, MUC16 includes a tandem domain consisting of 156 amino acid random repeats and 16 repeat regions containing sea urchin sperm protein, enterokinase and arginine (referred to as SEA domain). This particular structure activates signaling pathways for certain tumor cell phenotypic changes. Studies have shown that the C-terminal domain of MUC16 can accelerate the migration, growth and metastasis of tumor cells and slow down the apoptosis of tumor cells. Under normal physiological conditions, MUC16 is expressed in the conjunctiva, upper respiratory tract, internal organs, body cavity mesothelium, intestinal epithelium, and reproductive organs, which acts to lubricate and protect the surface of organs. It is also overexpressed in a variety of malignant tumors.
Figure 1. Model for MUC16-induced NK cell inhibition. (Felder, M., et al. 2014)
Immunization of MUC16 on Ovarian Cancer Cells
It is suggested that MUC16 can prevent the interaction between NK cells and target cells, and the killing effect of NK cells needs to be in direct contact with target cells, releasing cytolytic granules and causing apoptosis. Studies have confirmed that NK cells are more effective in binding and lysing ovarian cancer cells that knock out the MUC16 gene. Ovarian cancer cells expressing MUC16 can escape the recognition of NK cells, thereby inhibiting the killing effect of NK cells on tumor cells.
The immune protection provided by MUC16 is beneficial to the further growth of ovarian cancer cells, which leads to the metastasis of ovarian cancer cells in the abdominal cavity. Studies have shown that down-regulating the expression of MUC16 can increase the sensitivity of epithelial ovarian cancer cells to genotoxic drugs. Studies have further confirmed that MUC16 prevents ovarian cancer cells from being killed by NK cell-mediated anti-tumor cytotoxicity. It was found that MUC16 can bind to NK cells, B lymphocytes and monocytes through the receptor Siglect-9 (Siglec-9 expressed in immune cells), thereby attenuating the body's anti-tumor immune response and possibly promoting the transfer of ovarian cancer cells into the abdominal cavity.
MUC16 and Diagnosis of Ovarian Cancer
MUC16 is a commonly used tumor marker for clinical diagnosis of ovarian epithelial cancer. Combined with vaginal ultrasonography, menopausal status and MUC16 expression levels can improve the sensitivity and specificity of ovarian malignancies. In healthy human serum, the concentration of MUC16 is generally considered to be less than 35 U/mL, while the concentration of MUC16 in the serum of patients with ovarian cancer is much higher than this value. Elevated levels of MUC16 are not only manifested in patients with ovarian malignant tumors, but also in other malignant tumors of the reproductive tract such as endometrial cancer and cervical cancer. In addition, patients with lung cancer, bladder cancer, breast cancer, and even digestive tract malignancies also have certain Elevation, clinically alone or in combination with human epididymis protein 4 (HE4) and ultrasonography for early screening and identification of ovarian cancer increases the sensitivity and specificity of the diagnosis.
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