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Myeloid Derived Suppressor Cells Migrate in Response to Flow and Lymphatic Endothelial Cell Interaction in the Breast Tumor Microenvironment

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dc.creator Roberts, LaDeidra Monét
dc.creator Perez, Matthew J.
dc.creator Balogh, Kristen N.
dc.creator Mingledorff, Garnett
dc.creator Cross, Janet V.
dc.creator Munson, Jennifer M.
dc.date 2022-06-23T18:51:15Z
dc.date 2022-06-23T18:51:15Z
dc.date 2022-06-18
dc.date 2022-06-23T12:12:24Z
dc.date.accessioned 2023-03-01T18:51:38Z
dc.date.available 2023-03-01T18:51:38Z
dc.identifier Roberts, L.M.; Perez, M.J.; Balogh, K.N.; Mingledorff, G.; Cross, J.V.; Munson, J.M. Myeloid Derived Suppressor Cells Migrate in Response to Flow and Lymphatic Endothelial Cell Interaction in the Breast Tumor Microenvironment. Cancers 2022, 14, 3008.
dc.identifier http://hdl.handle.net/10919/110908
dc.identifier https://doi.org/10.3390/cancers14123008
dc.identifier.uri http://localhost:8080/xmlui/handle/CUHPOERS/281531
dc.description At the site of the tumor, myeloid derived suppressor cells (MDSCs) infiltrate and interact with elements of the tumor microenvironment in complex ways. Within the invading tumor, MDSCs are exposed to interstitial fluid flow (IFF) that exists within the chronic inflammatory tumor microenvironment at the tumor–lymphatic interface. As drivers of cell migration and invasion, the link between interstitial fluid flow, lymphatics, and MDSCs have not been clearly established. Here, we hypothesized that interstitial fluid flow and cells within the breast tumor microenvironment modulate migration of MDSCs. We developed a novel 3D model to mimic the breast tumor microenvironment and incorporated MDSCs harvested from 4T1-tumor bearing mice. Using live imaging, we found that sorted GR1+ splenocytes had reduced chemotactic index compared to the unsorted population, but their speed and displacement were similar. Using our adapted tissue culture insert assay, we show that interstitial fluid flow promotes MDSC invasion, regardless of absence or presence of tumor cells. Coordinating with lymphatic endothelial cells, interstitial fluid flow further enhanced invasion of MDSCs in the presence of 4T1 cells. We also show that VEGFR3 inhibition reduced both MDSC and 4T1 flow response. Together, these findings indicate a key role of interstitial fluid flow in MDSC migration as well as describe a tool to explore the immune microenvironment in breast cancer.
dc.description Published version
dc.format application/pdf
dc.format application/pdf
dc.language en
dc.publisher MDPI
dc.rights Creative Commons Attribution 4.0 International
dc.rights http://creativecommons.org/licenses/by/4.0/
dc.title Myeloid Derived Suppressor Cells Migrate in Response to Flow and Lymphatic Endothelial Cell Interaction in the Breast Tumor Microenvironment
dc.title Cancers
dc.type Article - Refereed
dc.type Text


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