title: Stem cell factor contributes to tumorigenesis of mast cells via an autocrine/paracrine mechanism.
abstract: Mastocytosis is a disease accompanied by the abnormal expansion and accumulation of mast cells. Although the D816V mutation is detected in most cases of systemic mastocytosis, the mutation is rarely observed in other forms of mastocytosis, such as cutaneous mastocytosis and mast cell leukemia/sarcoma, for which the mechanism of tumorigenesis remains unknown. In this study, we demonstrated a novel mechanism of mast cell tumorigenesis via SCF autocrine/paracrine release. SCF was highly expressed in a WT KIT-expressing HRMC line, contributing to the phosphorylation of KIT. Neutralization of external SCF using a neutralizing antibody or suppression of SCF production by RNA interference inhibited the growth of HRMC cells, indicating the essential role of SCF in cell proliferation. To the best of our knowledge, this is the first report to determine the significant contribution of SCF autoproduction to neoplastic proliferation of mast cells. These results indicate the possibility that targeting SCF production may become a novel treatment for mast cell malignancies.
authors.affiliation: Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Amagai
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Matsuda
authors.forename: K
authors.initials: K
authors.lastname: Jung
authors.forename: K
authors.initials: K
authors.lastname: Ohmori
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D019898:Autocrine Communication; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology*; D008415:Mastocytosis / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000378:metabolism*
chemical_list: D019089:Stem Cell Factor