title: CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell subsets of hematopoietic and nonhematopoietic origin.
abstract: CUB-domain-containing protein 1 (CDCP1) is a novel transmembrane molecule that is expressed in metastatic colon and breast tumors as well as on the surface of hematopoietic stem cells. In this study, we used multiparameter flow cytometry and antibodies against CDCP1 to analyze the expression of CDCP1 on defined hematopoietic cell subsets of different sources. In addition, CDCP1 expression on leukemic blasts and on cells with nonhematopoietic stem/progenitor cell phenotypes was determined. Here we demonstrate that a subset of bone marrow (BM), cord blood (CB), and mobilized peripheral blood (PB) CD34+ cells expressed this marker and that CDCP1 was detected on CD34(+)CD38- BM stem/progenitor cells but not on mature PB cells. Analysis of leukemic blasts from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia in blast crisis revealed that CDCP1 is predominantly expressed on CD34(+)CD133+ myeloid leukemic blasts. However, CDCP1 was not strictly correlated with CD34 and/or CD133 expression, suggesting that CDCP1 is a novel marker for leukemia diagnosis. Stimulation of CD34+ BM cells with CDCP1-reactive monoclonal antibody CUB1 resulted in an increased (approximately twofold) formation of erythroid colony-forming units, indicating that CDCP1 plays an important role in early hematopoiesis. Finally, we show that CDCP1 is also expressed on cells phenotypically identical to mesenchymal stem/progenitor cells (MSCs) and neural progenitor cells (NPCs). In conclusion, CDCP1 is not only a novel marker for immature hematopoietic progenitor cell subsets but also unique in its property to recognize cells with phenotypes reminiscent of MSC and NPC.
authors.affiliation: University of Tübingen, Department of Internal Medicine II, Division of Hematology, Immunology, Oncology and Rheumatology, Tübingen, Germany. hans-joerg.buehring@med.uni-tuebingen.de
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Bühring
authors.forename: Selim
authors.initials: S
authors.lastname: Kuçi
authors.forename: Tim
authors.initials: T
authors.lastname: Conze
authors.forename: Gisa
authors.initials: G
authors.lastname: Rathke
authors.forename: Kerol
authors.initials: K
authors.lastname: Bartolović
authors.forename: Frank
authors.initials: F
authors.lastname: Grünebach
authors.forename: Marwa
authors.initials: M
authors.lastname: Scherl-Mostageer
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Norbert
authors.initials: N
authors.lastname: Schweifer
authors.forename: Reiner
authors.initials: R
authors.lastname: Lammers
mesh_terms: D000071916:AC133 Antigen; D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D000951:Antigens, Neoplasm; D015415:Biomarkers; D001853:Bone Marrow / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D015415:Biomarkers; C432044:CDCP1 protein, human; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1