Intermittent Hypoxia-induced Changes in Tumor-associated Macrophages and Tumor Malignancy in a Mouse Model of Sleep Apnea
Open accessAbstract
Rationale: An increased cancer aggressiveness and mortality have been recently reported among patients with obstructive sleep apnea (OSA). Intermittent hypoxia (IH), a hallmark of OSA, enhances melanoma growth and metastasis in mice. Objectives: To assess whether OSA-related adverse cancer outcomes occur via IH-induced changes in host immune responses, namely tumor-associated macrophages (TAMs). Measurements and Main Results: Lung epithelial TC1 cell tumors were 84% greater in mice subjected to IH for 28 days compared with room air (RA). In addition, TAMs in IH-exposed tumors exhibited reductions in M1 polarity with a shift toward M2 protumoral phenotype. Although TAMs from tumors harvested from RA-exposed mice increased TC1 migration and extravasation, TAMs from IH-exposed mice markedly enhanced such effects and also promoted proliferative rates and invasiveness of TC1 cells. Proliferative rates of melanoma (B16F10) and TC1 cells exposed to IH either in single culture or in coculture with macrophages (RAW 264.7) increased only when RAW 264.7 macrophages were concurrently present. Conclusions: Our findings support the notion that IH-induced alterations in TAMs participate in the adverse cancer outcomes reported in OSA.
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HIFs can switch tumor-associated macrophages from an antitumorigenic M1-like phenotype to a protumorigenic M2-like phenotype.
“HIFs can also switch tumor‐associated macrophages (TAMs) from an antitumorigenic (M1‐like) phenotype to a protumorigenic (M2‐like) phenotype.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [120]
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- Authors
- Almendros, I., Wang, Y., Becker, L., Lennon, F. E., Zheng, J., Coats, B. R., Schoenfelt, K. S., Carreras, A., Hakim, F., Zhang, S. X., Farré, R., & Gozal, D.
- Affiliations
- Comer Children's Hospital (US)
- University of Chicago (US)
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona-IDIBAPS, Barcelona, Spain; and
- Corresponding author
- Gozal, David
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-03-01
- Volume
- 189
- Issue
- 5
- Pages
- 593-601
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- PMC
- PMC3977714
- OpenAlex
- W2122150741
- Cited by
- 201
- References
- 48
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 14 · 2023: 12 · 2022: 15 · 2021: 12 · 2020: 24 · 2019: 22 · 2018: 15 · 2017: 21 · 2016: 19 · 2015: 19 · 2014: 8
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Generalitat de Catalunya
- Ministerio de Economía y Competitividad (SAF2011-22576)
- Sociedad Española de Neumología y Cirugía Torácica
- National Institutes of Health (5t32dk087703-05)
- National Heart, Lung, and Blood Institute (HL-107160, R01HL086662, HL086662, HL-65 270, P50HL107160, R01HL065270)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32-DK-087703)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Keywords
- intermittent hypoxia, obstructive sleep apnea, tumor-associated macrophages, tumor malignancy, M2 macrophage polarization, macrophage polarization, tumor cell migration, tumor invasion, melanoma, tumor microenvironment, tumor immunology
- MeSH terms
- Animals, Hypoxia, Disease Models, Animal, Flow Cytometry, Lung Neoplasms, Macrophages, Male, Melanoma, Experimental, Mice, Inbred C57BL, Neoplasm Invasiveness, Phenotype, T-Lymphocytes, Cytotoxic, Sleep Apnea, Obstructive, Cell Line, Tumor, Cell Proliferation, Mice
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