Molecular mechanisms underlying the heterogeneous barrier responses of two primary endothelial cell types to sphingosine-1-phosphate

Salminen, Alec T.; McCloskey, Molly C.; Ahmad, Sarfraz; Romanick, Samantha; Chen, Kaihua; Houlihan, William J.; Klaczko, Michael E.; Flax, Jonathan; Waugh, Richard E.; McGrath, James L.

doi:10.1016/j.ejcb.2022.151233

Cited by 3 publications

(3 citation statements)

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“…In a comparison of LAM expression kinetics between HUVECs, glomerular endothelial cells, and dermal microvascular endothelial cells, each cell type had significant differences in response to tumor necrosis factor-α (TNFα) and interferon gamma (IFNγ) stimulation ( Figure 3 ) ( 28 ). Another recent study from our lab demonstrated differential barrier responses of HUVECs compared to human pulmonary microvascular endothelial cells in response to barrier modulating molecule, sphingosine-1-phosphate ( Figure 3 ) ( 68 ). Both studies highlight the limitations of this model for representing tissue-specific vascular barriers.…”

Section: Endothelial Cellsmentioning

confidence: 87%

“…While HUVECs are desensitized to TNFα following S1P exposure (i), HPMEC barriers are further disrupted (ii). Adapted from ( 68 ), used under Creative Commons CC BY-NC-ND license. ( D ) In vitro comparison of the response of three human cell lines, HUVECs, glomerular endothelial cells (GEC), and dermal microvascular endothelial cells (MvE), to TNFα and IFNγ stimulation.…”

Section: Endothelial Cellsmentioning

confidence: 99%

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Sourcing cells for in vitro models of human vascular barriers of inflammation

McCloskey

Zhang²,

Ahmad³

et al. 2022

Front. Med. Technol.

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The vascular system plays a critical role in the progression and resolution of inflammation. The contributions of the vascular endothelium to these processes, however, vary with tissue and disease state. Recently, tissue chip models have emerged as promising tools to understand human disease and for the development of personalized medicine approaches. Inclusion of a vascular component within these platforms is critical for properly evaluating most diseases, but many models to date use “generic” endothelial cells, which can preclude the identification of biomedically meaningful pathways and mechanisms. As the knowledge of vascular heterogeneity and immune cell trafficking throughout the body advances, tissue chip models should also advance to incorporate tissue-specific cells where possible. Here, we discuss the known heterogeneity of leukocyte trafficking in vascular beds of some commonly modeled tissues. We comment on the availability of different tissue-specific cell sources for endothelial cells and pericytes, with a focus on stem cell sources for the full realization of personalized medicine. We discuss sources available for the immune cells needed to model inflammatory processes and the findings of tissue chip models that have used the cells to studying transmigration.

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Section: Endothelial Cellsmentioning

confidence: 87%

Section: Endothelial Cellsmentioning

confidence: 99%

Sourcing cells for in vitro models of human vascular barriers of inflammation

McCloskey

Zhang²,

Ahmad³

et al. 2022

Front. Med. Technol.

Self Cite

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“…Platelets are typically attracted to activated or damaged ECs, and so these platelet-bound cancer cell complexes will be attracted to pre-metastatic niches with this type of damage. These platelets will also facilitate extravasation by the localized release of high concentrations of the bioactive lipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), both of which will increase EC permeability [ 77 , 78 , 79 , 80 , 81 ]. LPA also accelerates a damaging inflammatory cycle associated with tumor growth and metastasis [ 82 , 83 ].…”

Section: Soil: the Breast Cancer Metastasis Sites And The Immune Envi...mentioning

confidence: 99%

Breast Tumor Metastasis and Its Microenvironment: It Takes Both Seed and Soil to Grow a Tumor and Target It for Treatment

Bonni,

Brindley,

Chamberlain

et al. 2024

Cancers

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Metastasis remains a major challenge in treating breast cancer. Breast tumors metastasize to organ-specific locations such as the brain, lungs, and bone, but why some organs are favored over others remains unclear. Breast tumors also show heterogeneity, plasticity, and distinct microenvironments. This contributes to treatment failure and relapse. The interaction of breast cancer cells with their metastatic microenvironment has led to the concept that primary breast cancer cells act as seeds, whereas the metastatic tissue microenvironment (TME) is the soil. Improving our understanding of this interaction could lead to better treatment strategies for metastatic breast cancer. Targeted treatments for different subtypes of breast cancers have improved overall patient survival, even with metastasis. However, these targeted treatments are based upon the biology of the primary tumor and often these patients’ relapse, after therapy, with metastatic tumors. The advent of immunotherapy allowed the immune system to target metastatic tumors. Unfortunately, immunotherapy has not been as effective in metastatic breast cancer relative to other cancers with metastases, such as melanoma. This review will describe the heterogeneic nature of breast cancer cells and their microenvironments. The distinct properties of metastatic breast cancer cells and their microenvironments that allow interactions, especially in bone and brain metastasis, will also be described. Finally, we will review immunotherapy approaches to treat metastatic breast tumors and discuss future therapeutic approaches to improve treatments for metastatic breast cancer.

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