Beta-Adrenergic stimulation is necessary but not sufficient to promote CIH-induced Multiple Myeloma progression

Abstract

Multiple myeloma (MM), a terminal cancer of bone marrow plasma cells, affects about 35,000 people yearly, and kills 13,000. The KaLwRij mouse model spontaneously develops pre-malignant myeloma disease (MGUS) and is receptive to myeloma development. In the C57BL/6 mouse model, chronic intermittent hypoxia allows lethal engraftment of malignant myeloma cells. Our central hypothesis is that myeloma susceptibility in both models is modulated by the sympathetic nervous system and beta-adrenergic receptor activation. 8 - week old C57BL/6 female mice were exposed to either propranolol, isoproterenol, or saline for 6 weeks. At week 2, mice were injected with either 5TGM1/GFP+ (MM) cells or saline. Heart rate and heart rate variability were collected using MouseOx and LabChart Pro to monitor expected drug effects. All animals were monitored for terminal paralysis. Bone marrow and spleen cells were harvested for qPCR analysis to quantify 5TGM1 cell proliferation. C57BL/6 mice did not have decreased survival when treated with isoproterenol, but propranolol was protective against CIH-induced MM susceptibility. Propranolol did not increase survival in KalwRij mice. In order for Multiple Myeloma to progress in the CIH mouse model, β2-adrenergic receptor activation is required but is not sufficient. This experiment can be used to understand the role of sympathetic nervous system stimulation and its contribution to MM engraftment and growth. Supported by NIH 1R56HL152365. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.