Early life provision of 12-HETE by neutrophils imprints self-renewing capacity on alveolar macrophages
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216531 | GEO | 2022/10/28
REPOSITORIES: GEO
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Project description:The goal of this study is to determine the role of the 12/15-lipoxygenase pathway in the development and maintenance of alveolar macrophages.
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Project description:Early life provision of 12-HETE by neutrophils imprints self-renewing capacity on alveolar macrophages
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Project description:Early life provision of 12-HETE by neutrophils imprints self-renewing capacity on alveolar macrophages
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Project description:IntroductionRecent data indicate a hierarchical organization of many solid cancers, including breast cancer, with a small number of cancer initiating cells (CICs) that have the ability to self-renew and exhibit multi-lineage potency. We, and others, have demonstrated that CICs in breast cancer and glioma are relatively resistant to ionizing radiation if compared to their non-tumorigenic counterparts. However, the extent of the remaining self-renewing capacity of CICs after fractions of radiation is currently unknown. We hypothesized that CICs, in contrast to their non-tumorigenic counterparts, not only survive fractions of ionizing radiation but also retain the CIC phenotype as defined by operational means.MethodsWe used two marker systems to identify breast CICs (CD24-/low/CD44high, or lack of proteasome activity) and performed sphere-forming assays after multiple clinical fractions of radiation. Lineage tracking was performed by membrane staining. Cell cycle distribution and RNA content were assessed by flow cytometry and senescence was assessed via beta-galactosidase staining.ResultsWe demonstrated that irradiated CICs survived and retained their self-renewal capacity for at least four generations. We show that fractionated radiation not only spared CICs but also mobilized them from a quiescent/G0 phase of the cell cycle into actively cycling cells, while the surviving non-tumorigenic cells were driven into senescence.ConclusionsThe breast CIC population retains increased self-renewal capacity over several generations and therefore, we conclude that increases in the number of CICs after sublethal doses of radiation have potential clinical importance. Prevention of this process may lead to improved clinical outcome.
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