Sialilated beta1,6 branched N-oligosaccharides modulate adhesion, chemotaxis and motility of melanoma cells: Effect on invasion and spontaneous metastasis properties.
B16BL6 cells, selected specifically for invasive characteristics from B16F10 mouse melanoma cells, displayed greater ability to metastasize to lungs and produced larger colonies than the parent cells, when injected intravenously. When the two cell lines were compared for surface beta1,6-branched N-oligosaccharides by flow cytometry using Leuco-Phyto-Heam-Agglutinin, B16BL6 were found to express significantly higher levels. Inhibition of the oligosaccharide expression, by treatment of the cells with swainsonine or antisense-N-acetyl glucosaminyl-transferase-V, significantly reduced metastasis and invasion (>50%). Further, inhibition of oligosaccharides on the molecules like beta1 integrin (one of the major carriers) caused 30-45% reduction in their adherence to extra-cellular-matrix components especially collagen IV and laminin, and chemotaxis towards fibronectin and matrigel. The inhibition also decreased haptotaxis by approximately 50% to fibronectin but surprisingly was enhanced towards laminin by approximately 75%. The cells on which the expression of these oligosaccharides was inhibited failed to exhibit the characteristic spontaneous metastasis and adhesion properties of B16BL6 cells. In none of the cases, however, the secretion of matrix-metallo-proteases correlated with oligosaccharide expression. Sialylation of surface oligosaccharides was found to be accompanied by even higher motility and adherence to the substrates. These results strongly support an important role of cell surface beta1,6-linked N-oligosaccharides, especially the sialylated derivatives, in the processes that influence invasion and metastasis.
Reddy
B V V G
BV
Biochemistry and Cell Biology, Advanced Center for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai 410 208, India.
Kalraiya
Rajiv D
RD
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D009368:Neoplasm Transplantation; D009844:Oligosaccharides / Q000378:metabolism*; D017026:Swainsonine / Q000494:pharmacology; D014162:Transfection
D019012:Integrin beta1; D009844:Oligosaccharides; D008666:Metalloendopeptidases; D019158:N-Acetylneuraminic Acid; D017026:Swainsonine