Konur, A., Kreutz, M., Knüchel, R., Krause, S. W. and Andreesen, Reinhard
(1996)
Three-dimensional co-culture of human monocytes and macrophages with tumor cells: analysis of macrophage differentiation and activation.
International journal of cancer. Journal international du cancer 66 (5), pp. 645-52.
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Abstract
Here we report on an experimental system for generating TAM in vitro by culturing human MO and MO-derived macrophages (MAC) within 3-dimensional multicellular tumor spheroids (MCS). MO as well as MO-derived MAC migrate into tumor spheroids and spread throughout the entire spheroid within 16 hr. In contrast, fibroblast-spheroids were not infiltrated. The regular expression of MAC ...
Abstract
Here we report on an experimental system for generating TAM in vitro by culturing human MO and MO-derived macrophages (MAC) within 3-dimensional multicellular tumor spheroids (MCS). MO as well as MO-derived MAC migrate into tumor spheroids and spread throughout the entire spheroid within 16 hr. In contrast, fibroblast-spheroids were not infiltrated. The regular expression of MAC maturation-associated antigens on infiltrating MO was suppressed within MCS of the undifferentiated bladder carcinoma line J82 with regard to carboxypeptidase M (CPM), MAX.3 antigen and CD105. However, MAC within spheroids of highly differentiated papillary RT4 cells failed only the single antigen CD51, whereas MAC expressed the complete maturation-associated phenotype within non-tumorigenic HCV29 spheroids. Interestingly, the suppressive effect of J82 carcinoma cells could only be observed in 3-dimensional but not in monolayer cultures. The J82-MCS induced suppression of CPM and MAX.3 expression was only seen to be operative on infiltrating blood MO: MO first differentiated for 2 days and subsequently co-cultured with J82-MCS showed normal expression of MAX.3 and CPM within the spheroid. Besides the modulation of MAC phenotype, the cytokine response of intraspheroidal MAC was analyzed: upon co-culture MO secreted high IL-1beta and IL-6 but low amounts of TNF-alpha as compared to MAC. This MO typical cytokine pattern remained constant for up to 8 days in culture, again indicating a disturbed MO to MAC maturation within tumor spheroids. In conclusion, a 3-dimensional interaction with tumor cells in vitro results in significant changes in the phenotype and function of the spheroid-associated MO and MAC.
Export bibliographical data
| Item type: | Article |
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| Date: | 1996 |
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| Institutions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
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| Identification Number: | | Value | Type |
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| 8647627 | PubMed ID | | 10.1002/(SICI)1097-0215(19960529)66:5<645::AID-IJC11>3.0.CO;2-3 | DOI |
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| Classification: | | Notation | Type |
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| Antigens, Neoplasm/analysis | MESH | | Base Sequence | MESH | | Cell Differentiation/physiology | MESH | | Coculture Techniques | MESH | | Cytokines/biosynthesis | MESH | | Humans | MESH | | Macrophage Activation/physiology | MESH | | Macrophages/metabolism | MESH | | Metalloendopeptidases/analysis | MESH | | Molecular Sequence Data | MESH | | Monocytes/cytology | MESH | | Phenotype | MESH | | Polymerase Chain Reaction | MESH | | RNA, Messenger/metabolism | MESH | | Spheroids, Cellular | MESH | | Transcription, Genetic | MESH | | Tumor Cells, Cultured | MESH | | Tumor Necrosis Factor-alpha/biosynthesis | MESH | | Urinary Bladder Neoplasms/pathology | MESH |
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| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine |
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| Status: | Published |
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| Refereed: | Yes, this version has been refereed |
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| Created at the University of Regensburg: | Yes |
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| Item ID: | 14302 |
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