Heterogeneous expression of the laminin-binding O-mannosyl glycan on α-dystroglycan in pancreatic cancer cell line MIA PaCa-2 and the correlation with cell properties.

α-Dystroglycan (α-DG) is a central component of the dystrophin-glycoprotein complex, with the characteristic O-mannosyl glycan modification, which binds to several extracellular matrix proteins such as laminin. Disruption in the synthesis of laminin-binding glycan on α-DG is related to muscular dystrophies. In addition, loss of this glycan is frequently observed in many cancers, including pancreatic ductal adenocarcinoma (PDAC), correlating with poor prognosis. However, the significance of this glycan in the pathology of cancer remains unclear. This study aimed to clarify the biological significance of laminin-binding O-mannosyl glycan on α-DG in PDAC cells. Since a tumor-derived cancer cell line consists of cells with diverse characteristics, we first obtained several single-cell-derived clones using MIA PaCa-2, a commonly used undifferentiated PDAC cell line, and found that the laminin-binding glycan modification level on α-DG differs among the various clones. The glycan modification level correlated well with the mRNA expression level of LARGE1, the enzyme that synthesizes the laminin-binding structure on the glycan. We analyzed several PDAC cell properties, such as cellular morphology, proliferation and migration/invasion abilities, and examined their correlation with the glycan modification. We found that a high level of laminin-binding O-mannosyl glycan modification on α-DG correlated with the elongated cell morphology, high invasion ability, and low membrane blebbing activity, and vice versa. Furthermore, manipulation of the laminin-binding O-mannosyl glycan synthesis confirmed that this glycan partially contributed to these properties. Overall, this study provides valuable insights into the roles of the laminin-binding glycan on α-DG in PDAC.