Resolvins suppress tumor growth and enhance cancer therapy. J Exp Med 2018 Jan 02;215(1):115-140
Date
12/02/2017Pubmed ID
29191914Pubmed Central ID
PMC5748851DOI
10.1084/jem.20170681Scopus ID
2-s2.0-85039971527 (requires institutional sign-in at Scopus site) 215 CitationsAbstract
Cancer therapy reduces tumor burden by killing tumor cells, yet it simultaneously creates tumor cell debris that may stimulate inflammation and tumor growth. Thus, conventional cancer therapy is inherently a double-edged sword. In this study, we show that tumor cells killed by chemotherapy or targeted therapy ("tumor cell debris") stimulate primary tumor growth when coinjected with a subthreshold (nontumorigenic) inoculum of tumor cells by triggering macrophage proinflammatory cytokine release after phosphatidylserine exposure. Debris-stimulated tumors were inhibited by antiinflammatory and proresolving lipid autacoids, namely resolvin D1 (RvD1), RvD2, or RvE1. These mediators specifically inhibit debris-stimulated cancer progression by enhancing clearance of debris via macrophage phagocytosis in multiple tumor types. Resolvins counterregulate the release of cytokines/chemokines, including TNFα, IL-6, IL-8, CCL4, and CCL5, by human macrophages stimulated with cell debris. These results demonstrate that enhancing endogenous clearance of tumor cell debris is a new therapeutic target that may complement cytotoxic cancer therapies.
Author List
Sulciner ML, Serhan CN, Gilligan MM, Mudge DK, Chang J, Gartung A, Lehner KA, Bielenberg DR, Schmidt B, Dalli J, Greene ER, Gus-Brautbar Y, Piwowarski J, Mammoto T, Zurakowski D, Perretti M, Sukhatme VP, Kaipainen A, Kieran MW, Huang S, Panigrahy DAuthor
Tadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Cell Line, Tumor
Cell Proliferation
Cytokines
Disease Models, Animal
Docosahexaenoic Acids
Humans
Inflammation Mediators
Macrophages
Melanoma, Experimental
Mice
Mice, Knockout
Mice, Transgenic
Neoplasms
Phagocytosis
Phosphatidylserines
Tumor Burden
Xenograft Model Antitumor Assays
