Quantitative fluorescent profiling of VEGFRs reveals tumor cell and endothelial cell heterogeneity in breast cancer xenografts.
Bottom Line: 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.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.
Affiliation: Department of Bioengineering, University of Illinois at Urbana Champaign, Urbana, Illinois, 61801.Show MeSH
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Mentions: Given that multiple-cell subpopulations are seen across the small tumor cell and small tEC, we sought to better characterize these distributions using mixture modeling. The log of the data follows a mixture of normal distributions, implying that the original data follow a lognormal distribution. These are illustrated in Figures 4 and 5: where the VEGFR1 and VEGFR2 distributions represent three-component mixtures indicating that there are three-cell subpopulations.
Affiliation: Department of Bioengineering, University of Illinois at Urbana Champaign, Urbana, Illinois, 61801.