MICROENVIRONMENTAL FACTORS REGULATE LY-6 A E EXPRESSION ON PYV-TRANSFORMED BALB/C 3T3 CELLS/

In previous studies non-lymphoid murine tumor cells were sorted by flo w cytometry, into 2 subpopulations. The one expressed high levels of t he T-cell activation protein Ly-6 A/E and the other low levels of this protein. High Ly-6 A/E expression was associated with very high tumor igenicity and metastatic phenotypes. Cells expressing low levels of th is protein expressed a significantly reduced malignancy phenotype as c ompared to unsorted tumor populations. In view of its direct (or indir ect) involvement in tumor progression we studied, in the present work, the regulation by microenvironmental factors of Ly-6 A/E expression o n A3C polyoma-virus transformed cells. Ligation of membrane Ly-6 A/E b y the corresponding monoclonal antibodies resulted in up-regulated exp ression of this protein. Similar results were obtained by exposing A3C cells to interferon-alpha. In contrast, exposing tumor cells to tumor necrosis factor-alpha or to the extracellular matrix protein laminin resulted in a down-regulation of Ly-6 A/E expression on these cells. T hese results provide an additional insight into the role microenvironm ental factors might play in tumor progression.