CDCP1 identifies a CD146 negative subset of marrow fibroblasts involved with cytokine production.

Autor: Iwata M; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Torok-Storb B; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Wayner EA; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Carter WG; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2014 Oct 02; Vol. 9 (10), pp. e109304. Date of Electronic Publication: 2014 Oct 02 (Print Publication: 2014).
DOI: 10.1371/journal.pone.0109304
Abstrakt: 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.
Databáze: MEDLINE