title: Glycosaminoglycan mimicry by COAM reduces melanoma growth through chemokine induction and function.
abstract: Chlorite-oxidized oxyamylose (COAM), a glycosaminoglycan mimetic and potent antiviral agent, provided significant growth reduction of syngeneic murine B16-F1 melanoma tumors. A single early dose (100 μg, into the site of tumor cell inoculation) was sufficient to establish a persistent effect over 17 days (resected tumor volume of 78.3 mm(3)  in COAM-treated mice compared to 755.2 mm(3)  in the control cohort, i.e., 89.6% reduction of tumor volumes). COAM was a much better antitumoral agent than the polyanionic glycosaminoglycan heparin. COAM retained its antitumoral effect in lymphopenic mice, reinforcing the idea of myeloid cell involvement. Massive recruitment of myeloid cells into dermal air pouches in response to COAM and their increased presence in early-treated tumors indicated that mainly CD11b(+)  GR-1(+)  myeloid cells were attracted by COAM to exert antitumoral effects. Leukocyte chemotaxis was mediated by the chemokine system through the induction in B16-F1 cells of mouse granulocyte chemotactic protein-2/CXCL6 upon COAM treatment. Thus, COAM constitutes a novel tool to study the role of innate immune cells in the initial stages of tumor development and an example that innate immunostimulating glycosaminoglycan mimicry may be exploited therapeutically.
authors.affiliation: Rega Institute for Medical Research, University of Leuven, Belgium.
authors.forename: Helene
authors.initials: H
authors.lastname: Piccard
authors.forename: Nele
authors.initials: N
authors.lastname: Berghmans
authors.forename: Eva
authors.initials: E
authors.lastname: Korpos
authors.forename: Chris
authors.initials: C
authors.lastname: Dillen
authors.forename: Ilse Van
authors.initials: IV
authors.lastname: Aelst
authors.forename: Sandra
authors.initials: S
authors.lastname: Li
authors.forename: Erik
authors.initials: E
authors.lastname: Martens
authors.forename: Sandra
authors.initials: S
authors.lastname: Liekens
authors.forename: Sam
authors.initials: S
authors.lastname: Noppen
authors.forename: Jo Van
authors.initials: JV
authors.lastname: Damme
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000688:Amylose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006025:Glycosaminoglycans / Q000378:metabolism*; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D018716:Molecular Mimicry; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018925:Chemokines; D005456:Fluorescent Dyes; D006025:Glycosaminoglycans; C002668:oxyamylose; D000688:Amylose