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Glycosaminoglycan mimicry by COAM reduces melanoma growth through chemokine induction and function
Author(s) -
Piccard Helene,
Berghmans Nele,
Korpos Eva,
Dillen Chris,
Aelst Ilse Van,
Li Sandra,
Martens Erik,
Liekens Sandra,
Noppen Sam,
Damme Jo Van,
Sorokin Lydia,
Opdenakker Ghislain
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26465
Subject(s) - chemokine , glycosaminoglycan , myeloid , cancer research , immunology , melanoma , chemotaxis , biology , immune system , microbiology and biotechnology , receptor , biochemistry
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.