α2-Heremans-Schmid
glycoprotein (human
fetuin) is one of numerous
serum proteins produced in the liver. Recently, the biological functions of
fetuin, such as calcification and
insulin resistance, have been clarified. However, these effects appear to be indirect, occurring through binding to other molecules. When equal amounts of
fetuin in sera were treated with
chymotrypsin, resistance to the
protease treatment was observed in patients with
pancreatic cancer, but not in normal volunteers. To investigate the molecular mechanism behind this resistance, gel-filtration chromatography was performed. The results revealed that high molecular types of
fetuin showed a resistance to
protease treatment. When
fetuin was purified from sera of patients with
pancreatic cancer and normal volunteers, certain types of
proteins, including
haptoglobin (which binds to
fetuin derived from
pancreatic cancer patients), were identified using mass spectrometry. Furthermore, the
oligosaccharide structures of
fetuin analyzed with
lectin microarray differed between
pancreatic cancer patients and normal volunteers. This macro/micro heterogeneity of
fetuin might contribute to
pancreatic cancer resistance to
chymotrypsin treatment.