title: Role of decorin in multiple myeloma (MM) bone marrow microenvironment.
abstract: Decorin is a small, leucine-rich proteoglycan found in the extracellular matrix of various connective tissues with potential effective tumor suppressive properties. Recent data suggest low levels of decorin in multiple myeloma (MM) patients compared to healthy volunteers, as well as in patients with osteolytic bone lesions compared to non-osteolytic lesions. In the present report, we investigated the role of decorin in the MM microenvironment or niche. Our data suggests that decorin is produced by osteoblasts (OBs) but not by MM cells. Furthermore, MM cells decrease OB-induced decorin secretion and this effect is mediated by CCL3. Importantly, neutralizing CCL3 from MM cells restores decorin levels in OBs as does proteasome inhibitors such as carfilzomib. These findings indicate that decorin may indirectly act as an antagonist to MM cell survival and that the interplay between MM and decorin may be an important target to explore in manipulating the tumor niche to inhibit tumorigenesis.
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Neeharika
authors.initials: N
authors.lastname: Nemani
authors.forename: Loredana
authors.initials: L
authors.lastname: Santo
authors.forename: Homare
authors.initials: H
authors.lastname: Eda
authors.forename: Diana
authors.initials: D
authors.lastname: Cirstea
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mishima
authors.forename: Chirayu
authors.initials: C
authors.lastname: Patel
authors.forename: Elizabeth
authors.initials: E
authors.lastname: O'Donnell
authors.forename: Andrew
authors.initials: A
authors.lastname: Yee
authors.forename: Noopur
authors.initials: N
authors.lastname: Raje
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D045744:Cell Line, Tumor; D058575:Decorin / Q000502:physiology*; D006801:Humans; D051379:Mice; D009101:Multiple Myeloma / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D058575:Decorin
keywords: CCL3; DECORIN; MULTIPLE MYELOMA; OSTEOBLASTS