Agents which modify colonial morphology of tumor cells also affect acid vesicle function and fibronectin deposition...

The tumor cell line U937A is motile, weakly plastic-adherent and forms large, loosely packed colonies in vitro and is invasive and metastatic in vivo. U937A/R, a mutant selected for resistance to killing by tumor necrosis factor (TNF), is less motile, more adherent and forms small, tightly packed colonies and is not invasive or metastatic. U937A and U937A/R also have differing cytoplasmic distributions of acid vesicles, and unlike U937A, U937A/R fails to deposit fibronectin into its extracellular matrix. In this study we have sought reagents that could convert "loose" U937A cells into the nonmetastatic, "tight" colonial phenotype. Six effective reagents were found: wheat germ agglutinin, phytohemagglutinin-L, dexamethasone, chloroquine, promethazine, and monensin. All 6 reagents caused swelling and/or redistribution of acid vesicles but phytohemagglutinin-L, dexamethasone, and monensin also reduced fibronectin deposition in the extracellular matrix. Therefore, these agents probably reduce motility by interference with recycling of cell surface receptors through acid vesicles and also in some cases by altering the extracellular matrix.