Hypoxia affects tumor cell invasiveness in vitro: the role of hypoxia-activated ligand HAL1/13 (Ku86 autoantigen).
We have recently identified and characterized a new adhesion ligand, HAL1/13 (hypoxia-activated ligand), which mediates the increase in leukocyte adhesion to endothelium under hypoxic conditions (J. Immunol. 155 (1995) 802-810). The HAL1/13 antigen was cloned and found to be identical to p86 subunit of Ku autoantigen. In this study we demonstrate that exposure of neuroblastoma and breast carcinoma cells to hypoxia results in upregulation of HAL1/13 surface expression, coincident with an increased ability of these tumor cells to invade endothelial monolayers, which could be partially attenuated by the anti-HAL1/13 antibody. Hypoxia also potentiated neuroblastoma and breast carcinoma cell transmigration through Matrigel filters. Anti-HAL1/13 antibody inhibited haptotactic locomotion of hypoxic tumor cells on laminin.
Ginis
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Stroke Branch, National Institute of Neurological Disorders and Stroke, NIH, Building 36, Room 4A03, Bethesda, MD 20892-4128, USA. ginis@ninds.nih.gov
Faller
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D034961:Antigens, Nuclear; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion; D015687:Cell Hypoxia; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D000072200:Ku Autoantigen; D007797:Laminin / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D018613:Microscopy, Confocal; D008962:Models, Theoretical; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000276:immunology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000378:metabolism; D015854:Up-Regulation
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D007797:Laminin; D008024:Ligands; D009687:Nuclear Proteins; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D010100:Oxygen