Infiltrative capacity of T leukemia cell lines: A distinct functional property coupled to expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1)

Abstract

Infiltrative capacity was found to distinguish separate T leukemia cell lines. Of seven T-cell lines four exhibited capacity
to infiltrate Matrigel. Analysis of infiltration was performed at the single-cell level throughout the Matrigel using a depth
meter. Further, we examined differences in migration capacity and metalloproteinase production between infiltrating and non-infiltrating
T-cell lines. The capacity to infiltrate was not directly correlated to the capacity to adhere to the Matrigel or to migrate
on/to extracellular matrix components. It is concluded that infiltration capacity does not simply reflect capacity to migrate
but represents a distinct functional property. The production of metalloproteinases and their inhibitors by the separate T-cell
lines was analyzed using rt PCR, biosynthetic labelling, zymography, immunoprecipitation and ELISA. All T-cell lines with
capacity to infiltrate produced matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) while
non-infiltrating cell lines did not express MMP-9. Expression of MMP-1, 2, 3, 10, 14 and 17 showed no correlation to capacity
to infiltrate. Analysis of infiltration in the presence of a metalloprotease inhibitor showed an increased number of cells
within the gel. This enhancement of infiltration suggests that the function of MMPs and/or their inhibitors in lymphocyte
infiltration is more complex than previously thought.