Irene Ginis

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.

Chapter 18 The Role of Phosphorylation in Phagocyte Activation

Publisher Summary There is active phosphorylation–dephosphorylation when phagocytes are stimulated by a variety of agonists, but the actual assignment of a particular kinase/phosphatase protein substrate pair in the mapping of an activation cascade has not been satisfactorily accomplished. This chapter discusses the rapid progress that has been made in this area of phagocyte cell biology and examines the most compelling evidence for phosphorylation control that has been established in the human neutrophil for the activation of the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, the enzymatic activity of the respiratory burst. Of the various soluble and particulate agonists that stimulate oxidase, phorbol ester, phorbol myristate acetate (PMA), is of most relevance, for its receptor, protein kinase C (PKC) represents an important phosphorylating activity that has offered a functional assessment of oxidase activation in intact cells.