Effect of anticancer agents on directional migration of malignant C3H mouse fibroblastic cells in vitro

Abstract

Invasion of malignant cells was considered as a target for therapy. The effect of various anticancer agents, which were known to permit or to prevent invasion in vitro, on the growth and on the directional migration of virally transformed malignant C3H mouse fibroblastic cells (MO4) was examined. The increase of the diameter of spheroidal aggregates of MO4 cells in individual shaker culture was used as an index of growth. The mean diameter of the circular area covered by cells migrating from an aggregate explanted on glass, the number of cells in the periphery of this area, the height of the central part of the aggregate, the microcinephotographic aspect of migrating cells, and the immunocytochemistry of the cytoplasmic microtubular complex were considered as indices of directional migration. Ionizing radiation (5,000 and 20,000 R), and 5-fluorouracil (0.1, 0.5, and 1 microgram/ml), known to permit invasion, inhibited growth but allowed directional migration. Nocodazole (0.1 and 1 microgram/ml), known to prevent invasion, interfered with both growth and directional migration. These observations showed that various agents which affected the growth of aggregates of MO4 cells had different effects on the directional migration of these cells; they suggested that proliferation and migration were unrelated cellular activities. The assay for directional migration of cells from a spheroidal aggregate explanted on glass is proposed for the screening of potential antiinvasive agents.