title: Role of the CXCL12-CXCR4 axis in the development of deep rectal endometriosis.
abstract: Immunological and angiogenetic factors enhance the implantation of endometrial cells in the peritoneal cavity. The aim of this work was to determine the role of the CXCL12-CXCR4 axis in the attraction and the peritoneal implantation of endometriotic stromal cells in deep infiltrating endometriosis (DIE). Biopsies of DIE nodules were obtained from 14 patients undergoing surgical treatment for DIE with low rectal involvement and from 12 patients without macroscopic endometriosis undergoing laparoscopy. CXCR4 expression was evaluated by Western blot analysis and flow cytometry in eutopic endometrial cells and DIE stromal cells in primary cultures derived from the biopsies. CXCL12-induced migration of DIE eutopic endometrial stromal cells was evaluated by transwell migration. CXCL12 was assayed in peritoneal fluids by ELISA. CXCR4 expression was higher in eutopic endometrial stromal cells than in control endometrial cells (p<0.05) and in DIE stromal cells (p<0.05). Eutopic endometrial stromal cells were more attracted by CXCL12 than control cells (p<0.01). CXCL12 was higher in DIE peritoneal fluids than in controls (p<0.05). CXCR4 was down-regulated in deep infiltrating endometriotic stromal cells. The CXCL12-CXCR4 axis plays a role in the attraction of eutopic endometrial cells into the peritoneal cavity, and the down-regulation of CXCR4 in resident endometriotic cells could cause their arrest in situ.
authors.affiliation: Laboratory of Immunology, EA 1833, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Department of Digestive and Endocrine Surgery, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Leconte
authors.affiliation: Laboratory of Immunology, EA 1833, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Chouzenoux
authors.affiliation: Laboratory of Immunology, EA 1833, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Nicco
authors.affiliation: Laboratory of Immunology, EA 1833, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Chéreau
authors.affiliation: Department of Pathology, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Arkwright
authors.affiliation: Laboratory of Immunology, EA 1833, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Department of Gynecology Obstetrics II and Reproductive Medicine, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Santulli
authors.affiliation: Laboratory of Immunology, EA 1833, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Weill
authors.affiliation: Department of Gynecology Obstetrics II and Reproductive Medicine, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Chapron
authors.affiliation: Department of Digestive and Endocrine Surgery, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Dousset
authors.affiliation: Laboratory of Immunology, EA 1833, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. Electronic address: frederic.batteux@cch.aphp.fr.
authors.forename: F
authors.initials: F
authors.lastname: Batteux
mesh_terms: D001202:Ascitic Fluid / Q000166:cytology; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000276:immunology*; D004715:Endometriosis / Q000276:immunology / Q000473:pathology*; D004717:Endometrium / Q000166:cytology* / Q000502:physiology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D019718:Receptors, CXCR4
keywords: CXCL12; CXCR4; Deep infiltrating endometriosis; Endometriosis