Stromal regulation of neutrophils during lung metastasis of breast cancer

Sarah Marsden

Document Type

Article

Publication Date

Summer 2018

JAX Location

In: Student Reports, Summer 2018, The Jackson Laboratory

Abstract

Neutrophils are white blood cells (WBCs) in the human body, which can have a dual role in tumor progression and metastasis. Neutrophils begin by being tumor-killing, but their behavior can shift to being tumor-promoting. Mesenchymal stem cells (MSCs), are stem cells found in some organs such as the Jung and bone marrow (BM) that may impact the role of neutrophils in tumor progression. Our hypothesis is that the functional changes that occur in the neutrophils are caused by tissue/organ-specific MSCs. In vitro, we first co-cultured WBCs obtained from tumor-free mice, with BM-MSCs and Jung MSCs. Then we isolated neutrophils and used Quantitative Real-Time PCR (qPCR) to test for the expression level of genes in the neutrophils. We also repeated the same experiment with tumor-bearing mice. We found in both experiments that neutrophils cocultured in lung MSCs had an upregulation of immunosuppressive, hypoxia, cell cycle, and extracellular matrix (ECM)-related genes and a downregulation of phagocytic genes, when compared to neutrophils co-cultured with BM-MSCs and no MSCs. This, together with previous findings, suggests that lung MSCs are responsible for the functional changes that occur in neutrophils.

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