期刊
CANCER LETTERS
卷 361, 期 1, 页码 233-239出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.03.010
关键词
Intermittent hypoxia; Macrophages; Adipose tissue; Inflammation; Polarization; Sleep apnea
类别
资金
- National Institutes of Health [HL-65270-12]
- Herbert T. Abelson Chair in Pediatrics
- Generalitat de Catalunya/Marie Curie Actions [2010 BP_A2 00023]
Intermittent hypoxia (IH)-induces alterations in tumor-associated macrophages (TAMs) that are associated with adverse cancer outcomes, as reported in patients suffering from sleep apnea. Adipose tissues (AT) and bone-marrow (BM)-derived cells are the inferred sources of macrophages infiltrating malignant tumors. Here, the sources of TAMs and the phenotypic changes induced by IH in the ipsilateral and contralateral AT were investigated by using a syngeneic murine solid tumor model (TC1). C57/B6 male mice were exposed to either IH or room air (RA) for 6 weeks, With TC1 cells being inoculated in the 2nd week. Macrophage content, phenotype and tissue origin were assessed in tumors, and ipsilateral and contralateral AT. IH induced a similar to 2.2-fold increase in TAM tumor infiltration. However, differential responses in the tumor ipsilateral and contralateral AT emerged: IH increased infiltration of preferentially M1 macrophages in contralateral AT, while reductions in macrophages emerged in ipsilateral AT and primarily consisted of the M2 phenotype. These changes were accompanied by reciprocal increases in resident and BM-derived TAMs in the tumor. IH-induced phenotypic alterations in AT macrophages surrounding the tumor and their increased infiltration within the tumor may contribute to the accelerated tumor progression associated with IH. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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