Abstract
The invasiveness of MCF-7 human mammary carcinoma cells was tested in vitro via confronting cultures with embryonic chick heart fragments. Invasive (e.g. MCF-7/6) and non-invasive (e.g. MCF-7/AZ) variants were detected. Automated image analysis of time-lapse video-microscopy recordings showed that the plasma membrane ruffling activity of the invasive MCF-7/6 variant was higher than the ruffling activity of the non-invasive MCF-7/AZ variant. Addition of all-trans-retinoic acid to the culture medium (10(-6) M) inhibited both invasion and ruffling of MCF-7/6 cells, while MCF-7/AZ cells became invasive and acquired an increased ruffling by the same type of treatment. A similar opposite effect on MCF-7 cells was not found after treatment with other ligands of the nuclear steroid/thyroid receptor superfamily. Triiodo-l-thyronine (up to 10(-5) M) and beta-oestradiol (up to 10(-6) M) did not alter the invasiveness of the cells, while dexamethasone (10(-6) M) and the pure anti-oestrogen ICI 164,384 inhibited both invasion and ruffling. Our data show that retinoic acid can modulate invasiveness in opposite directions.
Highlights
Histological analysis of confronting cultures between MCF-7 cell aggregates and precultured heart fragments (PHF) revealed a striking difference in invasiveness between MCF-7/AZ and MCF-7/6 cells
The difference in invasiveness between the MCF-7 variants was evident in sections stained with hematoxylineosin, and could be demonstrated even better after immunohistochemical detection of chick heart antigens (Figure 1)
This difference did not depend on the type of culture medium, since confrontations in each other type of medium did not alter the interaction of the MCF-7 variants with PHF
Summary
CellsMCF-7 cells are human mammary carcinoma cells. MCF-7/ AZ cells were obtained from Dr P. Copenhagen, Denmark, and maintained in Eagle's Minimum Essential Medium (Flow, Irvine, Scotland) supplemented with 0.05% glutamine (w/v), 6 ng ml-' bovine insulin, 250 IU ml-' penicillin and 5% foetal bovine serum. Rochefort (Unite d'Endocrinologie Cellulaire et Moleculaire, Montpellier, France), and maintained in Dulbecco's modification of Eagle's Medium/Ham F12 50:50 (Flow) supplemented with 0.05% glutamine (w/v), 250 IU ml 1' penicillin, 100 fig ml-' streptomycin and 10% foetal bovine serum. Transmission electron micrographs showed similar characteristics as those described for MCF-7 cells by Seibert et al (1983) and by Vic et al (1982). Both MCF-7 variants had not been subjected to genetic manipulation nor to any deliberate epigenetic selection pressure
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