Peter A. Ward

Thrombospondin production and thrombospondin-mediated adhesion in U937 cells

U937 cells have low levels of surface thrombospondin (TSP) under control conditions but express higher levels after treatment for 1 day with 100 nM phorbol myristate acetate (PMA). Increased surface expression is due, in part, to increased biosynthesis. Untreated U937 cells do not adhere to TSP-coated plastic culture dishes but adhere strongly to TSP after stimulation with PMA. Untreated U937 cells also adhere weakly to endothelial cell monolayers while PMA-treated U937 cells attach strongly to monolayers of rat pulmonary artery endothelial cells. Endothelial cell adhesion appears to be mediated, in part, by TSP since antibodies to TSP partially inhibit.

The Attraction of Wandering Metastatic Cells

The cascade of events leading to the formation of metastases from primary tumors is a complex and incompletely understood phenomenon. The current concept envisions the initial invasion of local tissue and separation of individual cells or small groups of cells from the primary tumor. The invading cells gain access to the blood vascular and/or lymphatic circulatory systems and are distributed throughout the body. Most of the cells which enter the circulation, however, are rapidly killed. Only a few go on to establish themselves at secondary sites and carry on the processes that lead to the formation of metastatic growths. These processes include attachment to the appropriate structures (i.e., either the vascular endothelial cells or the sub-endothelial basement membranes), invasion of these structures and ultimately, proliferation. The process of tumor cell invasion through the endothelial layer and the sub-endothelial cell basement membrane most likely involves both active cell motility and substrate degradation.