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.
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Authors | Helene Piccard, Nele Berghmans, Eva Korpos, Chris Dillen, Ilse Van Aelst, Sandra Li, Erik Martens, Sandra Liekens, Sam Noppen, Jo Van Damme, Lydia Sorokin, Ghislain Opdenakker |
Journal | International journal of cancer
(Int J Cancer)
Vol. 131
Issue 4
Pg. E425-36
(Aug 15 2012)
ISSN: 1097-0215 [Electronic] United States |
PMID | 21953247
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 UICC. |
Chemical References |
- Chemokines
- Fluorescent Dyes
- Glycosaminoglycans
- oxyamylose
- Amylose
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Topics |
- Amylose
(analogs & derivatives, pharmacology)
- Animals
- Cell Division
(drug effects)
- Chemokines
(biosynthesis)
- Flow Cytometry
- Fluorescent Dyes
- Glycosaminoglycans
(metabolism)
- Male
- Melanoma, Experimental
(metabolism, pathology)
- Mice
- Mice, Nude
- Molecular Mimicry
- Real-Time Polymerase Chain Reaction
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