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Yin, S.* ; Wang, N.* ; Riabov, V.* ; Mossel, D.M.* ; Larionova, I.* ; Schledzewski, K.* ; Trofimova, O.* ; Sevastyanova, T.* ; Zajakina, A.* ; Schmuttermaier, C.* ; Gratchev, A.* ; Flatley, A. ; Kremmer, E. ; Zavyalova, M.* ; Cherdyntseva, N.* ; Simon-Keller, K.* ; Marx, A.* ; Klueter, H.* ; Goerdt, S.* ; Kzhyshkowska, J.*

SI-CLP inhibits the growth of mouse mammary adenocarcinoma by preventing recruitment of tumor-associated macrophages.

Int. J. Cancer 146, 1396-1408 (2020)
Verlagsversion Forschungsdaten DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Chitinase-like proteins (CLP) are chitin-binding proteins that lack chitin hydrolyzing activity, but possess cytokine-like and growth factor-like properties, and play crucial role in intercellular crosstalk. Both human and mice express two members of CLP family: YKL-40 and stabilin-1 interacting chitinase-like protein (SI-CLP). Despite numerous reports indicating the role of YKL-40 in the support of angiogenesis, tumor cell proliferation, invasion and metastasis, the role of its structurally related protein SI-CLP in cancer was not reported. Using gain-of-function approach, we demonstrate in the current study that the expression of recombinant SI-CLP in mouse TS/A mammary adenocarcinoma cells results in significant and persistent inhibition of in vivo tumor growth. Using quantitative immunohistochemistry, we show that on the cellular level this phenomenon is associated with reduced infiltration of tumor-associated macrophages (TAMs), CD4+ and FoxP3+ cells in SI-CLP expressing tumors. Gene expression analysis in TAM isolated from SI-CLP-expressing and control tumors demonstrated that SI-CLP does not affect macrophage phenotype. However, SI-CLP significantly inhibited migration of murine bone-marrow derived macrophages and human primary monocytes toward monocyte-recruiting chemokine CCL2 produced in the tumor microenvironment (TME). Mechanistically, SI-CLP did not affect CCL2/CCR2 interaction, but suppressed cytoskeletal rearrangements in response to CCL2. Altogether, our data indicate that SI-CLP functions as a tumor growth inhibitor in mouse breast cancer by altering cellular composition of TME and blocking cytokine-induced TAM recruitment. Taking into consideration weak to absent expression of SI-CLP in human breast cancer, it can be considered as a therapeutic protein to block TAM-mediated support of breast tumor growth.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Breast Cancer ; Ccl2 ; Chitinase-like Proteins ; Si-clp ; Tumor Microenvironment ; Tumor-associated Macrophages; Human Monoclonal-antibody; Chemokine Ligand 2; Carlumab Cnto 888; Ccl2 Blockade; Cancer; Progression; Cells; Glycoprotein; Inflammation; Therapies
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Zeitschrift International Journal of Cancer
Quellenangaben Band: 146, Heft: 5, Seiten: 1396-1408 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)