Thrombospondin 1 promotes tumor macrophage recruitment and enhances tumor cell cytotoxicity of differentiated U937 cells
- PMID: 18757424
- PMCID: PMC2562557
- DOI: 10.1158/0008-5472.CAN-08-0643
Thrombospondin 1 promotes tumor macrophage recruitment and enhances tumor cell cytotoxicity of differentiated U937 cells
Abstract
Inhibition of tumor growth by thrombospondin (TSP) 1 is generally attributed to its antiangiogenic activity, but effects on tumor immunity should also be considered. We show that overexpression of TSP1 in melanoma cells increases macrophage recruitment into xenograft tumors grown in nude or beige/nude mice. In vitro, TSP1 acutely induces expression of plasminogen activator inhibitor-1 (PAI-1) by monocytic cells, suggesting that TSP1-induced macrophage recruitment is at least partially mediated by PAI-1. Tumor-associated macrophages (TAM) can either promote or limit tumor progression. The percentage of M1-polarized macrophages expressing inducible nitric oxide synthase is increased in TSP1-expressing tumors. Furthermore, soluble TSP1 stimulates killing of breast carcinoma and melanoma cells by IFN-gamma-differentiated U937 cells in vitro via release of reactive oxygen species. TSP1 causes a significant increase in phorbol ester-mediated superoxide generation from differentiated monocytes by interaction with alpha(6)beta(1) integrin through its NH(2)-terminal region. The NH(2)-terminal domain of TSP2 also stimulates monocyte superoxide production. Extracellular calcium is required for the TSP1-induced macrophage respiratory burst. Thus, TSP1 may play an important role in antitumor immunity by enhancing recruitment and activation of M1 TAMs, which provides an additional selective pressure for loss of TSP1 and TSP2 expression during tumor progression.
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References
-
- Stenina OI, Byzova TV, Adams JC, McCarthy JJ, Topol EJ, Plow EF. Coronary artery disease and the thrombospondin single nucleotide polymorphisms. Int J Biochem Cell Biol. 2004;36:1013–30. - PubMed
-
- Crawford SE, Stellmach V, Murphy-Ullrich JE, et al. Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell. 1998;93:1159–70. - PubMed
-
- Isenberg JS, Romeo MJ, Abu-Asab M, et al. Increasing survival of ischemic tissue by targeting CD47. Circ Res. 2007;100:712–20. - PubMed
-
- Roberts DD. Regulation of tumor growth and metastasis by thrombospondin-1. Faseb J. 1996;10:1183–91. - PubMed
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