Differential expression of a gene signature for scavenger/lectin receptors by endothelial cells and macrophages in human lymph node sinuses, the primary sites of regional metastasis
J-H Martens
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
These authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
J Kzhyshkowska
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
These authors contributed equally to this work.
Department of Dermatology, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1–3, 68167 Mannheim, Germany.Search for more papers by this authorM Falkowski-Hansen
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorK Schledzewski
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorA Gratchev
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorU Mansmann
Biometry and Bioinformatics IBE, Medical School LMU München, Germany
Search for more papers by this authorC Schmuttermaier
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorE Dippel
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorW Koenen
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorF Riedel
Department of Otolaryngology, and Head and Neck Surgery, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorM Sankala
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Search for more papers by this authorK Tryggvason
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Search for more papers by this authorL Kobzik
Department of Environmental Health, Harvard School of Public Health, Boston, USA
Search for more papers by this authorG Moldenhauer
German Cancer Research Centre, Heidelberg, Germany
Search for more papers by this authorS Goerdt
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorJ-H Martens
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
These authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
J Kzhyshkowska
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
These authors contributed equally to this work.
Department of Dermatology, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1–3, 68167 Mannheim, Germany.Search for more papers by this authorM Falkowski-Hansen
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorK Schledzewski
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorA Gratchev
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorU Mansmann
Biometry and Bioinformatics IBE, Medical School LMU München, Germany
Search for more papers by this authorC Schmuttermaier
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorE Dippel
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorW Koenen
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorF Riedel
Department of Otolaryngology, and Head and Neck Surgery, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorM Sankala
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Search for more papers by this authorK Tryggvason
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Search for more papers by this authorL Kobzik
Department of Environmental Health, Harvard School of Public Health, Boston, USA
Search for more papers by this authorG Moldenhauer
German Cancer Research Centre, Heidelberg, Germany
Search for more papers by this authorS Goerdt
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
Search for more papers by this authorAbstract
Sentinel lymph node biopsy for several cancers has shown that metastatic tumour cells are preferentially arrested in the lymph node sinuses. To study the molecular components of this sinusoidal trap, gene profiling of lymph node (sinuses) versus tonsil (no sinuses) was performed. Among other groups of molecules, an intriguing gene signature of scavenger and lectin-like receptors was identified. Nine of the 13 genes were preferentially expressed in sinusoidal cells by immunohistochemistry. Using stabilin-2 and monoclonal antibody 3A5 as exclusive endothelial cell (EC) and macrophage (Mφ) markers, respectively, lymph node sinusoidal ECs (stabilin-2+, LYVE-1+, DC-SIGNR+, MARCO+, stabilin-1+, MMR+) and sinusoidal Mφ (MMR+, DC-SIGN+, sialoadhesin+, CD163+, stabilin-1+ ) showed distinct, but overlapping expression patterns of the signature molecules by double labelling immunofluorescence. The number of stabilin-1+ sinusoidal Mφ, however, varied considerably between samples, indicating turnover/differentiation dynamics in this sinusoidal cell population. In the hepatic sinuses, LYVE-1 and CD36 were strongly up-regulated on both sinusoidal ECs and Mφ, while DC-SIGNR and DC-SIGN were strongly down-regulated; in contrast to lymph node sinusoidal ECs, MARCO was confined to Mφ (Kupffer cells) in the liver sinuses. As Mφ are not present in the wall and lumen of splenic sinuses, splenic sinuses expressed a considerably reduced repertoire of scavenger/lectin receptors lacking sialoadhesin, CD36, CD163, and MARCO; in addition, DC-SIGNR was absent from splenic sinusoidal ECs, while DC-SIGN and thrombomodulin were strongly expressed. Interestingly, most of the signature molecules are known to mediate tumour cell adhesion in addition to their functions as scavenger or pattern recognition receptors. This study establishes a gene and tissue database platform to test the hypothesis that additive expression of the lymph node sinus signature genes in sinusoidal ECs and Mφ may contribute to selective tumour cell metastasis in lymph nodes and liver including organ-specific mechanisms, such as intraluminal retention or transmigration, while sparing the spleen. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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