Changes to N-linked oligosaccharide chains of human serum immunoglobulin G and matrix metalloproteinase-2 with cancer progression.
BACKGROUND
Alterations to the sugar chain structure of E-cadherin, a calcium-dependent adhesion molecule, have been shown to influence cancer metastasis. Furthermore, expression of sialyl Le(x) sugar chains on cancer cells has been demonstrated to influence their adhesion to vascular endothelial cells. On the other hand, matrix metalloproteinase-2 (MMP-2) degrades extracellular matrix and is involved in the invasion and metastasis of cancer cells.


METHODS
N-linked oligosaccharides of human serum immunoglobulin G (IgG) were analyzed in 36 patients with localized or metastatic cancer (12 lung, 12 gastric and 12 prostate cancer) and 10 healthy controls using fluorophore-associated carbohydrate electrophoresis (FACE). MMP-2 levels in the sera were determined by enzyme immunoassay.


RESULTS
Fr1 (monogalactosyl IgG oligosaccharide) and Fr2 (digalactosyl IgG oligosaccharides) were significantly decreased (p < 0.001), while Fr4 (agalactosyl IgG oligosaccharides) were significantly increased (p < 0.001) with cancer metastasis. The Fr4/Fr1+Fr2 ratio in localized and metastatic cancer was significantly increased compared to healthy controls (p < 0.001), and was significantly higher in metastatic than localized cancer (p < 0.001). Serum MMP-2 levels in metastatic cancer were significantly higher than in localized cancer (p < 0.001). There was a good correlation between the Fr4/Fr1+Fr2 ratio and serum MMP-2 levels in patients with metastatic cancer (p < 0.0001).


CONCLUSIONS
The analysis of serum IgG N-linked oligosaccharide chain structures by FACE may be an auxiliary indicator of serum tumor markers useful for monitoring cancer progression.
Department of Laboratory Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Yuhsaku
Y
Kanoh
Tadashi
T
Ohara
Tomoaki
T
Tadano
Motonari
M
Kanoh
Tohru
T
Akahoshi
D018450:Disease Progression; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D009369:Neoplasms / Q000097:blood*; D009844:Oligosaccharides / Q000737:chemistry*
D007074:Immunoglobulin G; D009844:Oligosaccharides; D020778:Matrix Metalloproteinase 2