Effects of retinoids and interferon‐gamma on cultured breast cancer cells in comparison with tumor necrosis factor alpha

Abstract

The combination of retinoic acid or tumor necrosis factor alpha (TNF-alpha) with interferon gamma (IFN-gamma) resulted in a synergistic amplification of the anti-proliferative effect of IFN-gamma on cultured breast cancer cells. Retinoic acid could be replaced by other biologically active retinoids. This synergism was also observed for the induction of 2'-5'-oligoadenylate-synthetase, an enzyme which is not expressed constitutively on BT-20 human breast cancer cells and not inducible by retinoic acid or TNF-alpha alone. However, both substances augmented the IFN-gamma-mediated expression. On the other hand, only TNF-alpha and not retinoic acid was able to increase the IFN-gamma induced expression of HLA-DR on the cell surface. Both cytokines antagonized the IFN-gamma effect on detachability of cultured BT-20 cells. The combinations of retinoic acid with IFN-gamma increased the down-regulation of specific binding sites for 125I-IFN-gamma. On the other hand, IFN-gamma exerted no effect on the concentration of the cytoplasmic binding protein for retinoic acid. Data obtained in this study demonstrate a different pattern of action between retinoic acid and TNF-alpha regarding their synergism in combination with IFN-gamma.

Modulation of Interferon (IFN)-inducible Gene Expression by Retinoic Acid

“…The mechanism of such augmentation is being investigated. Lastly, augmentation of IFN action by RA may not be due to enhancement of IFN receptors because both in breast tumor cells and embryonic tumor cells, which differentiate in response to RA, no increase in the affinity or number of IFN receptors was noted in RA-treated cells (29,30).…”

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

“…[37][38][39][40] However, a recent study using high-dose 13-cis RA treatment after myeloablative therapy and autologous bone marrow transplantation showed encouraging results. 41 Since differentiation and/or growth arrest induced by RA, TPA or vitamin D 3 was shown to be potentiated by IFN-␥ in several cell types, [42][43][44][45][46][47] the aim of our investigation was to determine whether IFN-␥ would synergize with RA or TPA to induce differentiation and growth inhibition in neuroblastoma cells.…”

“…41 Studies of cell types other than neuroblastoma have demonstrated that IFN-␥ potentiates differentiation and/or growth arrest induced by RA or vitamin D 3 in acute promyelocytic leukemia and myelomonocytic tumor cells [42][43][44][45] and in mammary and cervical carcinoma cells. 46,47 This raises the question whether "differentiation therapy" for neuroblastomas can be improved by combined treatment with IFN-␥ and RA or other agents known to influence their growth and differentiation. Indeed, combined treatment with RA and IFN-␥ in 1 human neuroblastoma cell line, LA-N-5, was reported to synergistically affect differentiation, growth inhibition and N-myc expression.…”

Prognostic Value of CD44 Splice Variant Expression in Ovarian Cancer

“…Human ovarian carcinoma cell lines were cultured under the con ditions previously described [22], CD44 surface expression was detected with a living cell radioimmunoassay as described by Grei ner et al [23]. In brief, about 25,000 cells were first seeded in 96-wcll tissue culture plates and after 24 h an attachment agent or the vehicle alone was added for incubation at 37 °C for 72 h. The culture medium was aspirated and 50 pi of E-MEM containing 10% BSA added before incubating at 37°C for 1 h. Thereafter, the plates were washed twice with E-MEM containing 1 % BSA.…”