Invasiveness and tumorigenicity of MO4 mouse fibrosarcoma cells pretreated with microtubule inhibitors

Abstract

MO4 cell aggregates with a diameter of 0.3 mm produced invasive fibrosarcomas after s.c. implantation into the pinna of syngeneic mice. Histology of pinnae fixed 10 min to 5 days after implantation of an aggregate suggested that the tumour was produced by the cells that invaded during the first day, and that the cells remaining in the aggregate were eliminated by the reaction of the host. Before implantation we have pretreated MO4 cell aggregates with 1 microgram/ml of the microtubule inhibitors Nocodazole (ND) and vincristine (VCR), known to inhibit both proliferation and invasion, and with 1 microgram/ml 5-fluorouracil (5-FU), known to inhibit proliferation but not invasion. Tumorigenicity was significantly reduced after treatment with ND or VCR, as compared to treatment with 5-FU or to controls. Histology of pinnae fixed 10 min to 3 days after implantation showed absence or scarceness of invasive MO4 cells after pretreatment with ND or VCR, in contrast with controls or with aggregates pretreated with 5-FU. The effect of ND, VCR and 5-FU on the growth of aggregates in culture on gyrotory shaker was reversible within 1 and 2 days respectively. After treatment with ND or VCR slight alterations in the function of the cytoplasmic microtubule complex remained visible during 3 days in cells migrating from an aggregate explanted on glass. Confrontation of pretreated aggregates with fragments of embryonic chick cardiac muscle in three-dimensional culture indicated that the anti-invasive effect of ND or VCR was reversible in vitro. We concluded that a delay of invasiveness caused by pretreatment with ND or VCR provided the host with the opportunity to eliminate MO4 cells implanted s.c. into the pinna.