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

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Summary

Methods

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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