Effects of human recombinant interferons-α2, -β and -γ on growth and survival of human cancer nodules maintained in continuous organotypic culture

Beaupain, R; Billard, Christian; Falcoff, E

doi:10.1016/0277-5379(86)90023-4

Cited by 16 publications

(12 citation statements)

References 16 publications

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“…As previously observed, IFN-p had no inhibitory effect on the growth of the A549 nodules [8]. The daily growth rates for 1.000 U/ml of IFN-P compared to control were 5.05 ± 0.11 and 5.6 ± 0.16%, re spectively, whereas the treatment with 1.000 U/ml of IFN-CI2 or -y resulted in a Fig.…”

Section: Resultssupporting

confidence: 77%

“…The methods to initiate and culture A549 nodules from monolayer cells have been previously described [8], A549 cells were derived from a human alveolar II pulmonary adenocarcinoma. The nodules, main tained in Petri dishes (Falcon 1006) on a 0.5% agar (Difco) semisolid culture medium with RPMI 1640 supplemented with 10% fetal calf serum (FCS), were transferred to Millipore filters (AABPO 2500, pore size 0.8 pm) for the experiments.…”

Section: Organotypic Culturementioning

confidence: 99%

“…All three IFNs were used alone or in combinations as follows: IFN-ct2, -p or -y (1,000 U/ml); IFN-a2 (1,000 U/ml) plus IFN-y (1,000 U/ml) or IFN-P (1,000 U/ml) plus IFN-y (1,000 U/ml). These concentrations of IFNs were de fined according to the efficiency observed in our pre vious studies [8,9]. Each experiment was done in duplicate.…”

Section: Ifn Treatment O F the Nodulesmentioning

confidence: 99%

“…IFN-a2, -P and -y [8], and (2) the synergistic effect of combina tions of IFN-CI2 and -y [9] on A549 human lung carcinoma cells maintained in organo typic culture [10]. This model accurately re flects the in vivo situation considering the stage of cell differentiation of the nodules which develop an alveolar structure and se crete pulmonary surfactant.…”

Section: Introductionmentioning

confidence: 99%

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Human Lung Cancer Nodules in Organotypic Culture: No Evidence of Correlation between the Antiproliferative Effects of Interferons and the Induction of 2′,5′-Oligoadenylate Synthetase

Martyré¹,

Beaupain²,

Falcoff³

1988

Tumor Biol

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Alveolar II pulmonary tumor cells (A549), maintained in continuous tridimen-sional organotypic culture, were used in an attempt to investigate whether there could be a relationship of the 2′,5′-oligoadenylate (2,5A) synthetase pathway to the antiproliferative activity of interferons (IFNs) in this particular tumor cell model. IFN-α₂ -β and -γ were used separately and in combinations. IFN- α₂ and -γ demonstrated an inhibitory effect on the nodule growth, whereas IFN- β did not. Moreover, combinations of IFN-α₂ and -γ resulted in a significant synergistic antiproliferative activity; IFN- β only potentiated slightly the effect of IFN-γ. All three IFNs induced an increase in the 2,5A synthetase activity, indicating a discrepancy with the pattern of anticellular activity. Furthermore, whereas the combination of IFN- α₂ and -γ resulted in a synergistic antiproliferative effect, no synergism was observed in the induction of the enzyme. These results show that there is a lack of correlation between the sensitivity or the resistance to IFNs of A549 tumor nodules and the induction of the 2,5A synthetase activity.

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Section: Resultssupporting

confidence: 77%

Section: Organotypic Culturementioning

confidence: 99%

Section: Ifn Treatment O F the Nodulesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human Lung Cancer Nodules in Organotypic Culture: No Evidence of Correlation between the Antiproliferative Effects of Interferons and the Induction of 2′,5′-Oligoadenylate Synthetase

Martyré¹,

Beaupain²,

Falcoff³

1988

Tumor Biol

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“…The infiltration area depended on the tumor cell type used and consequently determined the sensitivity to the cytolytic effect of LAK cells. More recently, we used a somewhat different threedimensional system [14,15]: organotypically cultivated breast carcinoma nodules and im mortalized benign mastosis nodules were co cultured with LAK cells [ 16], LAK cells pene trated actively into the two types of nodules, and they established close cell-to-cell contacts with both types of transformed mammary cells. Proliferation was inhibited more in the carcinoma nodules than in the mastosis nod ules after coculturing.…”

Section: Introductionmentioning

confidence: 99%

Interactions of Lymphokine-Activated Killer Cells and A549 Lung Carcinoma Nodules Maintained in Three-Dimensional Culture

Gharib¹,

Tamboise²,

Tamboise³

et al. 1997

Tumor Biol

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Lymphokine-activated killer (LAK) cells were cocultured in the presence of interleukin-2 (IL-2), with pulmonary surfactant secreting A549 lung carcinoma nodules and maintained in continuous three-dimensional culture for 2–6 days in an attempt to test the response of tumor cells which produce LAK cell inhibitory substances. The A549 nodules secrete mucus which envelops them. This mucus is also secreted inside pseudoalveolar structures characteristic of these nodules. The mucus contains the pulmonary surfactant and sialomu-cins, both LAK cell inhibitory substances. The spontaneous infiltration into the neoplastic tissue and the membrane contacts established between the two cell types were studied by means of histological, immunohistochemical and electron-microscopic methods. Free-floating LAK cells were allowed to sediment and adhere freely to the nodule surface. The cytostatic and cytolytic effects of LAK cells were tested using thymidine incorporation into DNA and flow cytometry. Despite the presence of a mucus envelope, LAK cells adhered to the A549 nodule surface and penetrated spontaneously into them in the presence of IL-2: they settled mainly in the pseudoalveolar structures where they became apoptotic. According to electron-microscopic observations performed on the second day of coculture, the LAK cells, which remained between the cancer cells, established mostly pinpoint contacts with the carcinoma cells, forming cytoplasmic fusions. These fusions indicate the induction of pores in both the cancer cell and the LAK cell membranes. Electron-microscopic observation also displayed LAK-cell-associated apoptotic and necrotic carcinoma cells. However, at this stage of the coculture (day 2), the DNA synthesis rate of the A549 nodules still remained unchanged; it diminished by approximately 3 times on day 4 and almost stopped on day 6: nodule disintegration was then complete. In the free-floating LAK cell component of the cocultures, DNA synthesis was already strongly inhibited (26 ×) by the second day. Nevertheless, their cytolytic effect remained unaltered, as was tested on A549 monolayer cells. The presence of tumor necrosis factor (TNF) in the coculture supernatant has been demonstrated, and when coculturing took place in the presence of monoclonal TNF antibody, nodule proliferation was significantly enhanced (up to 145%). Our results indicate that, despite the presence of pulmonary surfactant and sialomucins containing mucus, LAK cells were capable of killing lung carcinoma cells in three-dimensional culture at an early stage of coculture (day 2) by direct cell-to-cell contact. Total nodule disintegration, however, was complete much later (on day 6), and taking into account the low amount of LAK cells in the cancer tissue, this seemed to be the result of an indirect effect implying, in particular, the presence of soluble TNF.

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Fibroblast‐mediated differentiation in human breast carcinoma cells (MCF‐7) grown as nodules IN VITRO

Brouty‐Boyé¹,

Mainguéné²,

Magnien³

et al. 1994

Intl Journal of Cancer

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The growth of cells in 3-dimensional form as nodules in vitro facilitates studies of in vivo cellular interactions. Taking advantage of this technique, human breast carcinoma cells (MCF-7) were co-cultured with stromal fibroblasts isolated from either normal or tumorous breast tissue to study the influence of such fibroblasts on tumor-cell growth and differentiation. Ten days after co-culture of carcinoma cells with fibroblasts from normal tissue at a 1:10 ratio, the size of nodules began to increase and stabilize by day 30 while the fibroblast number decreased and finally disappeared. Concurrently, the carcinoma cells underwent a progressive redifferentiation process which histologically resulted in the appearance of highly developed papillar and tubular structures after 2 months in culture. The production of mucins was further evidence that these cells had undergone differentiation. By contrast, when MCF-7 cells were grown alone or with fibroblasts isolated from a breast carcinoma, the nodules continued to exhibit their characteristic histodedifferentiation properties and did not grow. The re-establishment of a normal epithelial state of differentiation in MCF-7 carcinoma nodules indicates that the phenotypic characteristics of tumor cells are reversible and are influenced or controlled by the stromal environment by which these tumor cells are surrounded or in contact with. Overall, our results open the possibility of exploiting the effects that connective tissue cells have on tumor-cell differentiation for use in prevention and treatment of cancer.

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Effects of human recombinant interferons-α2, -β and -γ on growth and survival of human cancer nodules maintained in continuous organotypic culture

Cited by 16 publications

References 16 publications

Human Lung Cancer Nodules in Organotypic Culture: No Evidence of Correlation between the Antiproliferative Effects of Interferons and the Induction of 2′,5′-Oligoadenylate Synthetase

Human Lung Cancer Nodules in Organotypic Culture: No Evidence of Correlation between the Antiproliferative Effects of Interferons and the Induction of 2′,5′-Oligoadenylate Synthetase

Interactions of Lymphokine-Activated Killer Cells and A549 Lung Carcinoma Nodules Maintained in Three-Dimensional Culture

Fibroblast‐mediated differentiation in human breast carcinoma cells (MCF‐7) grown as nodules IN VITRO

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Effects of human recombinant interferons-α2, -β and -γ on growth and survival of human cancer nodules maintained in continuous organotypic culture

Cited by 16 publications

References 16 publications

Human Lung Cancer Nodules in Organotypic Culture: No Evidence of Correlation between the Antiproliferative Effects of Interferons and the Induction of 2&prime;,5&prime;-Oligoadenylate Synthetase

Human Lung Cancer Nodules in Organotypic Culture: No Evidence of Correlation between the Antiproliferative Effects of Interferons and the Induction of 2&prime;,5&prime;-Oligoadenylate Synthetase

Interactions of Lymphokine-Activated Killer Cells and A549 Lung Carcinoma Nodules Maintained in Three-Dimensional Culture

Fibroblast‐mediated differentiation in human breast carcinoma cells (MCF‐7) grown as nodules IN VITRO

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Human Lung Cancer Nodules in Organotypic Culture: No Evidence of Correlation between the Antiproliferative Effects of Interferons and the Induction of 2′,5′-Oligoadenylate Synthetase

Human Lung Cancer Nodules in Organotypic Culture: No Evidence of Correlation between the Antiproliferative Effects of Interferons and the Induction of 2′,5′-Oligoadenylate Synthetase