Tumor cell surface carbohydrate and the metastatic phenotype

Area of Science:

• Cell Biology
• Glycobiology
• Cancer Research

Background:

• Cell surface carbohydrate synthesis is developmentally regulated and influences cell-cell interactions.
• Specific oligosaccharide structures on malignant cells may be essential for the metastatic phenotype.

Purpose of the Study:

• To investigate if specific oligosaccharide structures on highly malignant cells are required for metastasis.
• To identify defects in oligosaccharide biosynthesis that affect the metastatic phenotype.

Main Methods:

• Isolated lectin-resistant tumor cell mutants with defects in oligosaccharide biosynthesis from the MDAY-D2 cell line.
• Grouped mutants into genetic complementation classes and compared metastatic ability and cell surface glycoconjugates.
• Utilized swainsonine, an inhibitor of Golgi alpha-mannosidase II, to study the effects on oligosaccharide synthesis and metastasis.

Main Results:

• Class 1 mutants, deficient in sialic acid and galactose, showed a significantly attenuated metastatic phenotype.
• A revertant of class 1 mutation regained both wild-type glycoconjugate profile and high metastatic potential.
• Swainsonine treatment dramatically reduced lung colony formation in vivo, despite not affecting tumor cell growth in vitro or in situ.

Conclusions:

• Specific sialylated N-linked oligosaccharides on metastatic tumor cells are required for the expression of the metastatic phenotype.
• The observed defects in oligosaccharide biosynthesis directly correlate with reduced metastatic potential.
• Targeting the synthesis of these specific oligosaccharides may offer a therapeutic strategy to inhibit cancer metastasis.