Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis.
We report the cloning and characterization of a cancer-associated cell membrane glycoprotein recognized by mAb NCC-3G10. The antibody showed strong reactivity to a wide variety of cancer cells, but only to a limited number of normal cells including lymphocytes, endothelial cells, and basal cells of stratified squamous epithelium. The cDNA for the antigen encodes 178 aa, which includes a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Transfection of the cDNA into PLC/PRF/5 liver cancer cells resulted in reduced cell-cell adhesiveness, based on both morphology and results of Ca(2+)-dependent cell aggregation assay. In transfected cells, E-cadherin was markedly decreased at the protein level in inverse proportion to the expression level of the antigen recognized by NCC-3G10, but not at the mRNA level. Aggregation of the antigen by NCC-3G10-coated beads triggered accumulation of actin, suggesting some interplay between this antigen and E-cadherin through actin. When metastatic ability was examined in severe combined immunodeficient mice by injecting PLC/PRF/5 cells into the spleen, the transfectants formed a markedly higher number of metastatic nodules in comparison with controls. We have named this cell membrane glycoprotein, which down-regulates E-cadherin and promotes metastasis, dysadherin.
Ino
Yoshinori
Y
Pathology Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Gotoh
Masahiro
M
Sakamoto
Michiie
M
Tsukagoshi
Kiyomi
K
Hirohashi
Setsuo
S
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007473:Ion Channels; D008099:Liver / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D009369:Neoplasms / Q000378:metabolism*; D016366:Open Reading Frames; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000199:Actins; D000911:Antibodies, Monoclonal; D015820:Cadherins; D018076:DNA, Complementary; C451410:FXYD5 protein, human; D006023:Glycoproteins; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D002118:Calcium