Cancers, Vol. 12, Pages 502: Obesity Promotes Cooperation of Cancer Stem-Like Cells and Macrophages to Enhance Mammary Tumor Angiogenesis
Cancers, Vol. 12, Pages 502: Obesity Promotes Cooperation of Cancer Stem-Like Cells and Macrophages to Enhance Mammary Tumor Angiogenesis
Cancers doi: 10.3390/cancers12020502
Authors:
Hillers-Ziemer
McMahon
Hietpas
Paderta
LeBeau
McCready
Arendt
Obesity is correlated with worsened prognosis and treatment resistance in breast cancer. Macrophage-targeted therapies are currently in clinical trials, however, little is known about how obesity may impact treatment efficacy. Within breast adipose tissue, obesity leads to chronic, macrophage-driven inflammation, suggesting that obese breast cancer patients may benefit from these therapies. Using a high fat diet model of obesity, we orthotopically transplanted cancer cell lines into the mammary glands of obese and lean mice. We quantified changes in tumor invasiveness, angiogenesis and metastasis, and examined the efficacy of macrophage depletion to diminish tumor progression in obese and lean mice. Mammary tumors from obese mice grew significantly faster, were enriched for cancer stem-like cells (CSCs) and were more locally invasive and metastatic. Tumor cells isolated from obese mice demonstrated enhanced expression of stem cell-related pathways including Sox2 and Notch2. Despite more rapid growth, mammary tumors from obese mice had reduced necrosis, higher blood vessel density, and greater macrophage recruitment. Depletion of macrophages in obese tumor-bearing mice resulted in increased tumor necrosis, re...
Source: Cancers - Category: Cancer & Oncology Authors: Hillers-Ziemer McMahon Hietpas Paderta LeBeau McCready Arendt Tags: Article Source Type: research
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