Journal article
Chronic intermittent hypoxia enhances disease progression in myeloma-resistant mice
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.316(5), pp.R678-R686
05/01/2019
DOI: 10.1152/ajpregu.00388.2018
PMCID: PMC6589607
PMID: 30892915
Abstract
Obesity is the only known modifiable risk factor for multiple myeloma (MM), an incurable cancer of bone marrow plasma cells. The mechanism linking the two is unknown. Obesity is associated with an increased risk of sleep apnea, which results in chronic intermittent hypoxia (CIH), and drives solid tumor aggressiveness. Given the link between CIH and solid tumor progression, we tested the hypothesis that CIH drives the proliferation of MM cells in culture and their engraftment and progression in vivo. Malignant mouse 5TGM1 cells were cultured in CIH, static hypoxia, or normoxia as a control in custom, gas-permeable plates. Typically MM-resistant C57BL/6J mice were exposed to 10 h/day CIH (AHI = 12/h), static hypoxia, or normoxia for 7 days, followed by injection with 5TGM1 cells and an additional 28 days of exposure. CIH and static hypoxia slowed the growth of 5TGM1 cells in culture. CIH-exposed mice developed significantly more MM than controls (67 vs. 12%,
= 0.005), evidenced by hindlimb paralysis, gammopathy, bone lesions, and bone tumor formation. Static hypoxia was not a significant driver of MM progression and did not reduce survival (
= 0.117). Interestingly, 5TGM1 cells preferentially engrafted in the bone marrow and promoted terminal disease in CIH mice, despite a lower tumor burden, compared with the positive controls. These first experiments in the context of hematological cancer demonstrate that CIH promotes MM through mechanisms distinct from solid tumors and that sleep apnea may be a targetable risk factor in patients with or at risk for blood cancer.
Details
- Title: Subtitle
- Chronic intermittent hypoxia enhances disease progression in myeloma-resistant mice
- Creators
- Mahmoud Ali - University of IowaSandeep Kowkuntla - University of IowaDerick J Delloro - University of IowaCsaba Galambos - University of Colorado DenverDeep Hathi - Washington University in St. LouisSiegfried Janz - University of IowaMonica Shokeen - Washington University in St. LouisChakrapani Tripathi - University of IowaHongwei Xu - University of IowaJisung Yuk - University of IowaFenghuang Zhan - University of IowaMichael H Tomasson - University of IowaMelissa L Bates - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.316(5), pp.R678-R686
- DOI
- 10.1152/ajpregu.00388.2018
- PMID
- 30892915
- PMCID
- PMC6589607
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Grant note
- P30 CA086862 / NCI NIH HHS R01 CA151354 / NCI NIH HHS
- Language
- English
- Date published
- 05/01/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Pathology; Fraternal Order of Eagles Diabetes Research Center; Holden Comprehensive Cancer Center; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984259658002771
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