Dissertation/Thesis Abstract

Metabolically Activated Macrophages Driven by Obesity Promote TNBC Progression
by Tiwari, Payal, Ph.D., The University of Chicago, 2018, 135; 10977084
Abstract (Summary)

Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Here, we show that obesity reprograms mammary adipose tissue macrophages to a pro-inflammatory metabolically-activated phenotype (MMe) that alters the niche to support tumor formation. Unlike pro-inflammatory M1 macrophages that antagonize tumorigenesis, MMe macrophages are pro-tumorigenic and represent the dominant macrophage phenotype in mammary adipose tissue of obese humans and mice. MMe macrophages release cytokines in an NADPH oxidase 2 (NOX2)-dependent manner that signal through glycoprotein 130 (GP130) on TNBC cells to promote stem-like properties including tumor formation. Deleting Nox2 in myeloid cells or depleting GP130 in TNBC cells attenuates obesity-augmented TNBC stemness. Moreover, weight loss reverses the effects of obesity on MMe macrophage inflammation and TNBC tumor formation. Our studies implicate MMe macrophage accumulation in mammary adipose tissue as a mechanism for promoting TNBC stemness and tumorigenesis during obesity.

Indexing (document details)
Advisor: Rosner, Marsha Rich
Commitee: Becker, Lev, Brady, Mathew, Macleod, Kay
School: The University of Chicago
Department: Cancer Biology
School Location: United States -- Illinois
Source: DAI-B 80/05(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Oncology
Keywords: Cancer stem cells, GP130, Macrophages, NOX2, Obesity, TNBC
Publication Number: 10977084
ISBN: 9780438756694
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