Development of a monolayer invasion assay for the discrimination and isolation of metastatic lymphoma cells.

A new in vitro invasion model system, based on monolayers of 10T1/2 fibroblastic mouse embryo cells, is presented. When inoculated onto such a confluent monolayer, cells from a nonmetastatic T-cell lymphoma line remained on top, whereas cells from metastatic derivative lines penetrated through the monolayer. Combined differential interference contrast and interference reflection microscopy were used to follow the relative vertical cell positions in the co-cultures. The number of underlying lymphoma cells per unit area can be used as a quantitative invasion index, allowing a systematic comparison between cell lines. Moreover, since the invasive cells could be recovered separately, this invasion system allowed the isolation of minor subpopulation of invasive cells from a 1000-fold excess of noninvasive cells.