Clusterin induces the secretion of TNF-α and the chemotactic migration of macrophages

Biochemical and Biophysical Research Communications
Young-Jun ShimBon-Hong Min

Abstract

Tumor associated macrophages are known to be closely linked with tumor progression and metastasis. On the other hand, clusterin is overexpressed in several tumor types and regarded as a putative tumor-promoting factor due to this overexpression and the subsequent induction of chemoresistance. In our previous study, clusterin was found to induce the expression of matrix metalloproteinase-9 (MMP-9) in macrophages, and MMP-9 is known to be essential for tumor cell migration and invasion via basement membrane breakdown. Because paracrine interactions between tumor cells and surrounding macrophages regulate metastasis, these findings raise the possibility that clusterin promotes the secretion of cytokines in macrophages in addition to MMP-9. Here, we demonstrate that clusterin upregulates the expressions of chemotactic cytokines, that is, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1β (MIP-1β), regulated upon activation, normal T cell expressed and secreted (RANTES), and tumor necrosis factor-α (TNF-α) in Raw264.7 macrophages. In particular, clusterin stimulated TNF-α secretion via the activations of ERK, JNK, and PI3K/Akt pathways in a time and dose-dependent manner. Furthermore, clusterin-induced TNF-α ...Continue Reading

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Citations

Dec 18, 2015·Biomolecular Concepts·Philipp RohneClaudia Koch-Brandt
Jan 17, 2015·Frontiers in Surgery·Tinte ItinteangSwee T Tan
Dec 15, 2016·Biochemical and Biophysical Research Communications·Young-Jun ShimBon-Hong Min
Jul 12, 2013·European Journal of Oral Sciences·Qalb-E-Saleem KhanHarald Osmundsen
Jan 31, 2014·American Journal of Physiology. Renal Physiology·Christopher Y C NguanCaigan Du
Aug 9, 2020·International Journal of Molecular Sciences·Drahomira HolmannovaZdenek Fiala
Mar 16, 2019·Frontiers in Neuroscience·Evangeline M FosterNoel J Buckley
Dec 20, 2018·Journal of Cellular Physiology·Jessika BertacchiniSandra Marmiroli
Mar 16, 2021·Frontiers in Immunology·Jennifer Wittwer, David Bradley

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