Three-dimensional culture and multidrug resistance: effects on immune reactivity of MCF-7 cells by monocytes.
BACKGROUND
Multicellular spheroids are known to be the most adapted model to keep the in vitro resistance properties of cells. This in vivo-like tissue-culture representation was applied to investigate the immune reactivity of MCF-7 cells by monocytes.


METHODS
Human blood monocytes, obtained by elutriation, were co-cultured with multicellular tumor spheroids of drug-sensitive (MCF-7S) and doxorubicin-resistant (MCF-7DXR) MCF-7 breast cancer cells.


RESULTS
Tumor cells, according to their phenotype, induced differential recruitment and behavior of the immune cells towards the two types of spheroids. The secretion of various cytokines and the expression of several adhesion molecules were analysed. The MCF-7DXR/monocytes co-culture supernatant showed higher levels of IL-6 and IL-8 than the MCF-7S/monocytes co-culture supernatant. Cells from the MCF-7DXR spheroids expressed some adhesion molecules, CD-44 and CD-54, leading to a strong cellular cohesion in comparison with the sensitive spheroids.


CONCLUSIONS
The two spheroid phenotypes represented an excellent model system for determining the precise tumor microenvironment in which cells move, the crucial molecular requirements and the mechanisms by which immunotherapeutic strategies could be developed to eradicate chemo-resistant tumors.
Mougel
Laurent
L
Laboratoire de Biochimie et Biologie Moléculaire EA-3306, UFR de Pharmacie, IFR 53 Biomolécules, 51096 Reims, France.
Tarpin
Michel
M
Albert
Philippe
P
Le Naour
Richard
R
Devy
Jérôme
J
Kaplan
Hervé
H
Ventéo
Lydie
L
Carlier
Annie
A
Madoulet
Claudie
C
D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D018432:Drug Resistance, Multiple; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018874:Spheroids, Cellular
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D016207:Cytokines