Journal article
The novel angiogenic inhibitor, angiocidin, induces differentiation of monocytes to macrophages
Cancer research (Chicago, Ill.), v 68(14), pp 5905-5914
15 Jul 2008
PMID: 18632645
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We previously showed that angiocidin, a tumor and vascular associated protein, is a potent inhibitor of angiogenesis and tumor growth. Angiocidin is a multidomain protein that exerts its antiangiogenic activity through multiple mechanisms, including effects on cell matrix interaction. Here, we describe another activity of angiocidin that may contribute to its antitumor activity. We show that angiocidin activates monocytes to secrete a mixture of proinflammatory cytokines and induces them to differentiate into macrophage-like cells. Using the monocytic cell line THP-1, we show that angiocidin induces the cells to become adherent and phagocytic, express macrophage markers, and secrete matrix metalloproteinase-9. Microarray analysis of control and angiocidin-treated THP-1 cells revealed that angiocidin up-regulated p105/p50, p100/p52, and rel B, components of the nuclear factor-kappa B (NF-kappa B) pathway. We confirmed the microarray data and showed that angiocidin induced phosphorylation of I kappa beta, p50, and p65 and translocation of p50 and p65 to the nucleus. We also showed that angiocidin activated up-stream mediators of NF-kappa B, such as the mitogen-activated protein kinase (MAPK) pathway and phosphoinositide-3 kinase (PI3K). Blockage of NF-kappa B and MAPK activation with small molecule inhibitors completely prevented angiocidin-mediated secretion of cytokines from THP-1 cells, but did not inhibit their adhesive phenotype. Blocking PI3K inhibited both secretion of cytokines, as well as the adhesive phenotype. These data suggest that angiocidin activates monocytes to secrete cytokines and differentiates them to a macrophage-like phenotype through at least two pathways mediated by MAPK and NF-kappa B, as well as PI3K.
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Details
- Title
- The novel angiogenic inhibitor, angiocidin, induces differentiation of monocytes to macrophages
- Creators
- Anita Gaurnier-Hausser - Temple UniversityVicki L. Rothman - Philadelphia UniversitySvetoslav Dimitrov - Philadelphia UniversityGeorge P. Tuszynski - Temple University
- Publication Details
- Cancer research (Chicago, Ill.), v 68(14), pp 5905-5914
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 10
- Grant note
- R01CA088931 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01 CA088931-03S1; R01 CA088931 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Intensive Medical Sciences (IMS)
- Web of Science ID
- WOS:000257768300049
- Scopus ID
- 2-s2.0-48649096366
- Other Identifier
- 991021930425704721
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- Web of Science research areas
- Oncology