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Tumor cell surface beta 1-6 branched oligosaccharides and lung metastasis
Y Lu1, J C Pelling, W G Chaney
1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha 68198-4525.
Abstract:
NIH3T3 cells transfected with an activated Ha-ras oncogene were treated with L-PHA, the leukoagglutinin from red kidney beans. Cell lines resistant to L-PHA-mediated cytotoxicity were isolated and found to contain reduced levels of L-PHA-binding oligosaccharides. The levels of N-acetylglucosaminyltransferase V, the enzyme responsible for the initiation of the beta 1-6 branch, were reduced in L-PHA-resistant cells. Tumorigenicity in nude mice was unchanged by the change in oligosaccharide expression, but the ability to form lung tumors after intravenous injection was significantly reduced. These results demonstrate that the ability of NIH3T3 cells transfected with an activated Ha-ras oncogene to form lung tumors after intravenous injection into nude mice is reduced in all six L-PHA selected cell lines containing a reduction in beta 1-6 branched Asn-linked oligosaccharides.
Insights
NIH3T3 cells with activated Ha-ras oncogene showed reduced lung tumor formation after L-PHA treatment. This reduction in lung metastasis was linked to decreased beta 1-6 branched oligosaccharides and N-acetylglucosaminyltransferase V activity.
Area of Science:
- Oncology
- Glycobiology
- Cell Biology
Background:
- Activated Ha-ras oncogene promotes tumorigenesis.
- Leukoagglutinin (L-PHA) from red kidney beans can mediate cytotoxicity.
- Oligosaccharide branching, particularly beta 1-6, plays roles in cell adhesion and metastasis.
Purpose of the Study:
- To investigate the role of L-PHA-binding oligosaccharides in Ha-ras-transformed NIH3T3 cell metastasis.
- To determine if reduced oligosaccharide branching affects tumor formation and metastasis in vivo.
Main Methods:
- NIH3T3 cells were transfected with an activated Ha-ras oncogene.
- Cells were treated with L-PHA to select for resistant cell lines.
- Levels of L-PHA-binding oligosaccharides and N-acetylglucosaminyltransferase V were analyzed.
- Tumorigenicity and lung metastasis were assessed in nude mice after intravenous injection.
Main Results:
- L-PHA-resistant cell lines exhibited reduced levels of L-PHA-binding oligosaccharides.
- N-acetylglucosaminyltransferase V activity was decreased in resistant cells.
- While overall tumorigenicity was unchanged, lung tumor formation after intravenous injection was significantly reduced.
- Six L-PHA selected cell lines showed reduced metastasis, correlating with decreased beta 1-6 branched Asn-linked oligosaccharides.
Conclusions:
- Reduced beta 1-6 branched Asn-linked oligosaccharides, mediated by decreased N-acetylglucosaminyltransferase V, significantly impair lung metastasis of Ha-ras-transformed NIH3T3 cells.
- Specific changes in cell surface oligosaccharide structure can impact the metastatic potential of cancer cells.
- Targeting glycosylation pathways may offer strategies to inhibit cancer metastasis.