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 flow cytometry, into 2 subpopulations. The one expressed high levels of the 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 tumorigenicity and metastatic phenotypes. Cells expressing low levels of this protein expressed a significantly reduced malignancy phenotype as compared to unsorted tumor populations. In view of its direct (or indirect) involvement in tumor progression we studied, in the present work, the regulation by microenvironmental factors of Ly-6 A/E expression on A3C polyoma-virus transformed cells. Ligation of membrane Ly-6 A/E by the corresponding monoclonal antibodies resulted in up-regulated expression 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. These results provide an additional insight into the role microenvironmental factors might play in tumor progression.