Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schledzewski, K; Falkowski, M; Moldenhauer, G; Metharom, P; Kzhyshkowska, J; Ganss, R; Demory, A; Falkowska-Hansen, B; Kurzen, H; Ugurel, S; Geginat, G; Arnold, B; Goerdt, S.
Lymphatic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1+, F4/80+, CD11b+ macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: implications for the assessment of lymphangiogenesis.
J Pathol. 2006; 209(1):67-77
Doi: 10.1002/path.1942
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Ugurel-Becker Selma
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- Abstract:
- Lymphangiogenesis is a novel prognostic parameter for several cancers that is preferentially quantified by immunohistochemistry of the lymphatic endothelium-specific hyaluronan receptor LYVE-1. Recently, the specificity of LYVE-1 was challenged by serendipitous observations of LYVE-1 expression in rare tissue macrophages. As expression of the hyaluronan receptor-like molecule stabilin-1 is shared by sinusoidal endothelium and macrophages, a thorough analysis of LYVE-1 expression was performed using macrophage-specific markers in vivo and in vitro. In murine tumour models and excisional wound healing, LYVE-1 expression occurred in a subset of CD11b(+), F4/80(+) tissue macrophages that preferentially co-expressed stabilin-1. Upon comparison of single- and double-labelling immunofluorescence, it became apparent that LYVE-1(+) macrophages mimic sprouting and collapsed lymphatic vessels. In vitro, LYVE-1 expression was induced in 25-40% of murine bone marrow-derived macrophages upon exposure to B16F1 melanoma-conditioned medium and IL-4/dexamethasone. By FACS analysis, 11.5% of bone marrow-derived macrophages were LYVE-1(+), stabilin-1(+) double-positive, while 9.9% were LYVE-1(+), stabilin-1(-) and 33.5% were LYVE-1(-), stabilin-1(+). Northern and western analyses confirmed expression of LYVE-1 mRNA and protein in bone marrow-derived macrophages. In the light of the current debate about true endothelial trans-differentiation versus endothelial mimicry of monocytes/macrophages, LYVE-1(+), stabilin-1(+) non-continuous endothelial-like macrophages will require further developmental and functional analyses. In conclusion, the findings imply that LYVE-1 staining must be supplemented by double labelling with macrophage markers in order to differentiate clearly between LYVE-1(+) lymphatics and LYVE-1(+) tumour-infiltrating macrophages. This improved approach will help to clarify the prognostic significance of lymphangiogenesis in malignant tumours.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigens, CD11b - analysis
- Antigens, Differentiation - analysis
- Bone Marrow Cells - metabolism
- Cell Adhesion Molecules, Neuronal - metabolism
- Cells, Cultured -
- Disease Models, Animal -
- Endothelium, Lymphatic - metabolism
- Female -
- Glycoproteins - metabolism
- Lymphangiogenesis - physiology
- Macrophages - metabolism Macrophages - physiology
- Melanoma - metabolism Melanoma - pathology Melanoma - secondary
- Membrane Glycoproteins - metabolism
- Mice -
- Mice, Inbred C57BL -
- Neoplasm Proteins - metabolism
- Tumor Cells, Cultured -
- Vesicular Transport Proteins -
- Wound Healing - physiology
- Find related publications in this database (Keywords)
- LYVE-1
- lymphangiogenesis
- stabilin-1
- endothelial-like
- macrophages