title: Expression pattern of the CXCL12/CXCR4-CXCR7 trio in Kaposi sarcoma skin lesions.
abstract: BACKGROUND
  Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma (KS).
  
  
  OBJECTIVE
  We investigated whether the CXCL12/CXCR4-CXCR7 protein trio could constitute KS biomarkers.
  
  
  METHODS
  Endothelial and spindle cells positive for CXCL12/CXCR4-CXCR7, human herpesvirus-8 latency-associated nuclear antigen (LANA), Ki67 antigen (proliferation) and vascular endothelial growth factor (VEGF) were quantitated in skin lesions from patients with AIDS-associated KS, patients with classic KS and patients with angiomas, using immunohistochemistry and quantitative image analysis (16, 21 and 20 skin lesions, respectively). Plasma CXCL12 concentrations were measured by enzyme-linked immunosorbent assay from 20 patients with AIDS-KS, 12 HIV-infected patients without KS and 13 healthy donors' samples.
  
  
  RESULTS
  Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS-associated KS and classic KS vs. angiomas (P < 0·001), and in nodular vs. macular/papular KS lesions (P < 0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection (r > 0·4; P < 0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS-associated KS, HIV-infected patients without KS, and healthy donors.
  
  
  CONCLUSIONS
  The CXCL12/CXCR4-CXCR7 trio is upregulated in KS and correlates with KS pathophysiological markers and the severity of skin lesions. Histological assessment of the CXCL12 axis could serve as a valuable biomarker for KS diagnosis and progression.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Département de Pharmaco-Toxicologie Clinique, Paris, France.|UMR996 - Inflammation, Chemokines and Immunopathology, INSERM, Université Paris-Sud, Université Paris-Saclay, 92140, Clamart, France.
authors.forename: A
authors.initials: A
authors.lastname: Desnoyer
authors.affiliation: Service de Dermatologie, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin, Paris, France.|Université Paris Descartes, UMR1016, Paris, France.|INSERM, UMR1016, Institut Cochin, Université Paris Descartes, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Dupin
authors.affiliation: Université Sorbonne UPMC, Université Paris 06, UMRS1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.|INSERM, UMRS1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Assoumou
authors.affiliation: Service d'Anatomopathologie, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Carlotti
authors.affiliation: UMR996 - Inflammation, Chemokines and Immunopathology, INSERM, Université Paris-Sud, Université Paris-Saclay, 92140, Clamart, France.
authors.forename: F
authors.initials: F
authors.lastname: Gaudin
authors.affiliation: UMR996 - Inflammation, Chemokines and Immunopathology, INSERM, Université Paris-Sud, Université Paris-Saclay, 92140, Clamart, France.|Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Service de Virologie, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Deback
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Département de Pharmaco-Toxicologie Clinique, Paris, France.|Université Paris Diderot, INSERM, IAME, UMR1137, Paris, France.|INSERM, IAME, UMR1137, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Peytavin
authors.affiliation: Université Sorbonne UPMC, Université Paris 06, UMRS1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.|INSERM, UMRS1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.|Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Virologie, Paris, France.
authors.forename: A G
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: UMR996 - Inflammation, Chemokines and Immunopathology, INSERM, Université Paris-Sud, Université Paris-Saclay, 92140, Clamart, France.|Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Service de Médecine Interne, Clamart, France.
authors.forename: F
authors.initials: F
authors.lastname: Boué
authors.affiliation: UMR996 - Inflammation, Chemokines and Immunopathology, INSERM, Université Paris-Sud, Université Paris-Saclay, 92140, Clamart, France.
authors.forename: K
authors.initials: K
authors.lastname: Balabanian
authors.affiliation: UMR996 - Inflammation, Chemokines and Immunopathology, INSERM, Université Paris-Sud, Université Paris-Saclay, 92140, Clamart, France.|Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Service de Maladies Infectieuses et Tropicales, France Sorbonne Universités, UPMC, Université Paris 06, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Pourcher
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000956:Antigens, Viral / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C501896:ACKR3 protein, human; D020533:Angiogenesis Inhibitors; D000956:Antigens, Viral; D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D009687:Nuclear Proteins; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; C109540:latency-associated nuclear antigen; D013792:Thalidomide; D000077269:Lenalidomide