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Quantitative fluorescent profiling of VEGFRs reveals tumor cell and endothelial cell heterogeneity in breast cancer xenografts.

ABSTRACT: Plasma membrane-localized vascular endothelial growth factor receptors (VEGFR) play a critical role in transducing VEGF signaling toward pro and antiangiogenic outcomes and quantitative characterization of these receptors is critical toward identifying biomarkers for antiangiogenic therapies, understanding mechanisms of action of antiangiogenic drugs, and advancing predictive computational models. While in vitro analysis of cell surface-VEGFRs has been performed, little is known about the levels of cell surface-VEGFR on tumor cells. Therefore, we inoculate nude mice with the human triple-negative breast cancer, MDA-MB-231, cell line; isolate human tumor cells and mouse tumor endothelial cells from xenografts; and quantitatively characterize the VEGFR localization on these cells. We observe 15,000 surface-VEGFR1/tumor endothelial cell versus 8200 surface-VEGFR1/tumor endothelial cell at 3 and 6 weeks of tumor growth, respectively; and we quantify 1200-1700 surface-VEGFR2/tumor endothelial cell. The tumor cell levels of VEGFR1 and VEGFR2 are relatively constant between 3 and 6 weeks: 2000-2200 surface-VEGFR1/tumor cell and ~1000 surface-VEGFR2/tumor cell. Cell-by-cell analysis provides additional insight into tumor heterogeneity by identifying four cellular subpopulations based on size and levels of cell membrane-localized VEGFR. Furthermore, when these ex vivo data are compared to in vitro data, we observe little to no VEGFRs on MDA-MB-231 cells, and the MDA-MB-231 VEGFR surface levels are not regulated by a saturating dose of VEGF. Overall, the quantification of these dissimilarities for the first time in tumor provides insight into the balance of modulatory (VEGFR1) and proangiogenic (VEGFR2) receptors.

SUBMITTER: Imoukhuede PI

PROVIDER: S-EPMC3987073 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Quantitative fluorescent profiling of VEGFRs reveals tumor cell and endothelial cell heterogeneity in breast cancer xenografts.

Imoukhuede Princess I PI Popel Aleksander S AS

Cancer medicine 20140122 2

Plasma membrane-localized vascular endothelial growth factor receptors (VEGFR) play a critical role in transducing VEGF signaling toward pro and antiangiogenic outcomes and quantitative characterization of these receptors is critical toward identifying biomarkers for antiangiogenic therapies, understanding mechanisms of action of antiangiogenic drugs, and advancing predictive computational models. While in vitro analysis of cell surface-VEGFRs has been performed, little is known about the levels ...[more]

PMID: 24449499

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Dataset Information

Quantitative fluorescent profiling of VEGFRs reveals tumor cell and endothelial cell heterogeneity in breast cancer xenografts.

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Quantitative fluorescent profiling of VEGFRs reveals tumor cell and endothelial cell heterogeneity in breast cancer xenografts.

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