title: CDCP1 identifies a CD146 negative subset of marrow fibroblasts involved with cytokine production.
abstract: In vitro expanded bone marrow stromal cells contain at least two populations of fibroblasts, a CD146/MCAM positive population, previously reported to be critical for establishing the stem cell niche and a CD146-negative population that expresses CUB domain-containing protein 1 (CDCP1)/CD318. Immunohistochemistry of marrow biopsies shows that clusters of CDCP1+ cells are present in discrete areas distinct from areas of fibroblasts expressing CD146. Using a stromal cell line, HS5, which approximates primary CDCP1+ stromal cells, we show that binding of an activating antibody against CDCP1 results in tyrosine-phosphorylation of CDCP1, paralleled by phosphorylation of Src Family Kinases (SFKs) Protein Kinase C delta (PKC-δ). When CDCP1 expression is knocked-down by siRNA, the expression and secretion of myelopoietic cytokines is increased. These data suggest CDCP1 expression can be used to identify a subset of marrow fibroblasts functionally distinct from CD146+ fibroblasts. Furthermore the CDCP1 protein may contribute to the defining function of these cells by regulating cytokine expression.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Mineo
authors.initials: M
authors.lastname: Iwata
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Beverly
authors.initials: B
authors.lastname: Torok-Storb
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Wayner
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: William G
authors.initials: WG
authors.lastname: Carter
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051929:CD146 Antigen / Q000032:analysis* / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D051745:Protein Kinase C-delta / Q000032:analysis / Q000276:immunology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019061:src-Family Kinases / Q000032:analysis / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051929:CD146 Antigen; C432044:CDCP1 protein, human; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D019061:src-Family Kinases; D051745:Protein Kinase C-delta