Altered melanoma cell surface glycosylation mediates organ specific adhesion and metastasis via lectin receptors on the lung vascular endothelium.
Adhesive interactions between the molecules on cancer cells and the target organ are one of the key determinants of the organ specific metastasis. In this communication we show that b1,6 branched N-oligosaccharides which are expressed in a metastasis-dependent manner on B16-melanoma metastatic cell lines, participate in the adhesion process. We demonstrate that high metastatic cells show significantly increased translocation of one of the major carriers of these oligosaccharides, lysosome associated membrane protein (LAMP1), to the cell surface. LAMP1 on high metastatic cells, carry very high levels of these oligosaccharides, which are further substituted with poly N-acetyl lactosamine (polylacNAc), resulting in the expression of high density of very high affinity ligands for galectin-3 on the cell surface. We show that galectin-3 is expressed in highest amount in the lungs as compared to other representative organs. Blocking galectin-3 by pre-incubating the frozen sections of the lungs with 100 mM lactose, substantially inhibited the adhesion of high metastatic cells, while pre-incubation with sucrose had no effect. Finally, by in situ labeling and immunoprecipitation experiment, we demonstrated that the lung vascular endothelial cells express galectin-3 constitutively on their surface. Galectin-3 on the organ endothelium could thus serve as the first anchor for the circulating cancer cells, expressing high density of very high affinity ligands on their surface, and facilitate organ specific metastasis.
Krishnan
Vaidehi
V
Institute of Molecular and Cell Biology, Singapore 117 609, Singapore.
Bane
Sanjay M
SM
Kawle
Poonam D
PD
Naresh
Kikkeri N
KN
Kalraiya
Rajiv D
RD
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D001681:Biological Assay; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism*; D006031:Glycosylation; D007785:Lactose / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D025942:Oligosaccharides, Branched-Chain / Q000032:analysis / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D021381:Protein Transport; D011975:Receptors, Mitogen / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology; D000267:Tissue Adhesions; D015854:Up-Regulation
D015703:Antigens, CD; D037502:Galectin 3; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D025942:Oligosaccharides, Branched-Chain; D011134:Polysaccharides; D011975:Receptors, Mitogen; D013395:Sucrose; C037199:poly-N-acetyllactosamine; D007785:Lactose