title: A subpopulation of circulating endothelial cells express CD109 and is enriched in the blood of cancer patients.
abstract: BACKGROUND
  The endothelium is not a homogeneous organ. Endothelial cell heterogeneity has been described at the level of cell morphology, function, gene expression, and antigen composition. As a consequence of the genetic, transcriptome and surrounding environment diversity, endothelial cells from different vascular beds have differentiated functions and phenotype. Detection of circulating endothelial cells (CECs) by flow cytometry is an approach widely used in cancer patients, and their number, viability and kinetic is a promising tool to stratify patient receiving anti-angiogenic treatment.
  
  
  RESULTS
  Currently CECs are identified as positive for a nuclear binding antigen (DNA+), negative for the pan leukocyte marker CD45, and positive for CD31 and CD146. Following an approach recently validated in our laboratory, we investigated the expression of CD109 on CECs from the peripheral blood of healthy subject and cancer patients. The endothelial nature of these cells was validated by RT-PCR for the presence of m-RNA level of CDH5 (Ve-Cadherin) and CLDN5 (Claudin5), two endothelial specific transcripts. Before treatment, significantly higher levels of CD109+ CECs and viable CD109+CECs were found in breast cancer patients and glioblastoma patients compared to healthy controls, and their number significantly decreased after treatment. Higher levels of endothelial specific transcripts expressed in developing endothelial cells CLEC14a, TMEM204, ARHGEF15, GPR116, were observed in sorted CD109+CECs when compared to sorted CD146+CECs, suggesting that these genes can play an important role not only during embryogenesis but also in adult angiogenesis. Interestingly, mRNA levels of TEM8 (identified as Antrax Toxin Receptor1, Antrax1) were expressed in CD109+CECs+ but not in CD146+CECs.
  
  
  CONCLUSIONS
  Taken together our results suggest that CD109 represent a rare population of circulating tumor endothelial cells, that play a potentially useful prognostic role in patients with glioblastoma. The role of CD109 expression in cancer vessel-specific endothelial cells deserves to be further investigated by gene expression studies.
authors.affiliation: Laboratory of Hematology-Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancuso
authors.affiliation: Laboratory of Hematology-Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Calleri
authors.affiliation: Laboratory of Hematology-Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gregato
authors.affiliation: Laboratory of Hematology-Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Labanca
authors.affiliation: Laboratory of Hematology-Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Quarna
authors.affiliation: Laboratory of Hematology-Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Antoniotti
authors.affiliation: Department of Neuro-Oncology, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Cuppini
authors.affiliation: Department of Neuro-Oncology, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Finocchiaro
authors.affiliation: Department of Neuro-Oncology, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Marica
authors.initials: M
authors.lastname: Eoli
authors.affiliation: Center for the Study and Treatment of Myelofibrosis, Research Laboratories of Biotechnology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.affiliation: Laboratory of Hematology-Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis* / Q000097:blood / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology; D051929:CD146 Antigen / Q000032:analysis / Q000097:blood / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis / Q000097:blood / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000097:blood / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000097:blood / Q000235:genetics; D009369:Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*
chemical_list: D015703:Antigens, CD; C120523:CD109 protein, human; D051929:CD146 Antigen; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins