FIBRINOGEN PROMOTES ADHESION OF MONOCYTIC TO HUMAN MESOTHELIOMA CELLS

Adhesion between monocytic and mesothelioma or pleural mesothelial cel ls influences stromal remodeling in pleural neoplasia. We found that c ultured monocytic cells (U937) adhere to either human pleural mesothel ioma (MS-1) or mesothelial (MeT5A) cells in vitro. I-125-fibrinogen bo und specifically and saturably to either cell line, and specific fibri nogen binding increased upon stimulation of these cells with proinflam matory agents such as phorbol myristate (PMA), lipopolysaccharide (LPS ) or tumor necrosis factor (TNF-alpha). We purified the fibrinogen rec eptor protein from a membrane fraction of MS-1 cells and identified it by immunoprecipitation as intercellular adhesion molecule (ICAM-1). A nti-ICAM-1 antibody or antisense oligonucleotides inhibited fibrinogen -mediated cell adhesion and binding of I-125-fibrinogen to mesotheliom a or mesothelial cells. Cultured monocytic cells adhere to either meso thelioma or mesothelial cells, and the interaction is promoted by fibr inogen binding ICAM-1 at the cell surface. ICAM-1 is expressed by meso thelioma cells and CD 11b by macrophages in the fibrinous mesothelioma tumor stroma. The data suggest a common mechanism by which monocytic cells could adhere to either malignant mesothelioma cells or the mesot helial surface in pleural neoplasia.