Three-dimensional co-culture of human monocytes and macrophages with tumor cells: Analysis of macrophage differentiation and activation

Konur, A and Kreutz, M and Knuchel, R and Krause, SW and Andreesen, R (1996) Three-dimensional co-culture of human monocytes and macrophages with tumor cells: Analysis of macrophage differentiation and activation. INTERNATIONAL JOURNAL OF CANCER, 66 (5). pp. 645-652. ISSN 0020-7136,

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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 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 nontumorigenic 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-1 beta 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. (C) 1996 Wiley-Liss, Inc.

Item Type: Article
Uncontrolled Keywords: NECROSIS-FACTOR-ALPHA; IL-6 GENE-EXPRESSION; MATURATION INVITRO; TNF-ALPHA; CANCER; ANTIGENS; RELEASE; HETEROGENEITY; INTERLEUKIN-1; MICROREGIONS;
Depositing User: Dr. Gernot Deinzer
Last Modified: 19 Oct 2022 08:35
URI: https://pred.uni-regensburg.de/id/eprint/51701

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