Mucin-16
Mucin-16 '' also known as Ovarian cancer-related tumor marker CA125 is a protein that in humans is encoded by the MUC16 gene. MUC-16 is a member of the mucin family glycoproteins. MUC-16 has found application as a tumor marker or biomarker that may be elevated in the blood of some patients with specific types of cancers, most notably ovarian cancer, or other conditions that are benign.
Structure
Mucin 16 is a membrane associated mucin that possesses a single transmembrane domain. A unique property of MUC16 is its large size. MUC16 is more than twice as long as MUC1 and MUC4 and contains about 22,000 amino acids, making it the largest membrane-associated mucin.MUC16 is composed of three different domains:
- An N-terminal domain
- A tandem repeat domain
- A C-terminal domain
Function
MUC16 is a component of the ocular surface, the respiratory tract and the female reproductive tract epithelia. Since MUC16 is highly glycosylated it creates a hydrophilic environment that acts as a lubricating barrier against foreign particles and infectious agents on the apical membrane of epithelial cells. Also, the cytoplasmic tail of MUC16 has been shown to interact with cytoskeleton by binding members of the ERM protein family. The expression of mucin 16 has been shown to be altered in dry eye, cystic fibrosis, and several types of cancers.Role in cancer
MUC16 has been shown to play a role in advancing tumorigenesis and tumor proliferation by several different mechanisms.As a biomarker
Testing of CA-125 blood levels has been proposed as useful in treating ovarian cancer. While the test can give useful information for women already known to have ovarian cancer, CA-125 testing has not been found useful as a screening method because of the uncertain correlation between CA-125 levels and cancer. In addition to ovarian cancer, CA-125 can be elevated in patients who have conditions such as endometrial cancer, fallopian tube cancer, lung cancer, breast cancer, and gastrointestinal cancer. It can also be increased in pregnant women. Because of the wide variety of conditions that can increase serum levels, CA-125 is not used to detect cancer, but it is often used to monitor responses to chemotherapy, relapse, and disease progression in ovarian cancer patients.Metastatic invasion
MUC16 is also thought to participate in cell-to-cell interactions that enable the metastasis of tumor cells. This is supported by evidence showing that MUC16 binds selectively to mesothelin, a glycoprotein normally expressed by the mesothelial cells of the peritoneum. MUC16 and mesothelin interactions are thought to provide the first step in tumor cell invasion of the peritoneum. The region consisting of 64 amino acids at the N-terminus of cell surface mesothelin has been experimentally established as the functional binding domain for MUC16/CA125. An immunoadhesin that consists of the IAB domain of mesothelin and the human Fc portion has the ability to disrupt the heterotypic cancer cell adhesion mediated by the MUC16-mesothelin interaction.Mesothelin has also been found to be expressed in several types of cancers including mesothelioma, ovarian cancer and squamous cell carcinoma. Since mesothelin is also expressed by tumor cells, MUC16 and mesothelial interactions may aid in the gathering of other tumor cells to the location of a metastasis, thus increasing the size of the metastasis.