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Near infrared imaging of Mer tyrosine kinase (MERTK) using MERi-SiR reveals tumor associated macrophage uptake in metastatic disease.

ABSTRACT: The receptor tyrosine kinase Mer (MERTK) is a promising drug target in cancer, where it can influence the metastasis-promoting signaling of both tumor cells and immune cells alike; however, no small molecule probes currently exist to selectively image Mer. In this work, we design and synthesize a selective near-infrared fluorescent molecular probe of Mer (MERi-SiR). Confocal microscopy of metastases in mice reveals predominant probe accumulation in Mer-expressing tumor-associated macrophages.

SUBMITTER: Miller MA

PROVIDER: S-EPMC5736449 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Near infrared imaging of Mer tyrosine kinase (MERTK) using MERi-SiR reveals tumor associated macrophage uptake in metastatic disease.

Miller Miles A MA Kim Eunha E Cuccarese Michael F MF Plotkin Alec L AL Prytyskach Mark M Kohler Rainer H RH Pittet Mikael J MJ Weissleder Ralph R

Chemical communications (Cambridge, England) 20171201 1

The receptor tyrosine kinase Mer (MERTK) is a promising drug target in cancer, where it can influence the metastasis-promoting signaling of both tumor cells and immune cells alike; however, no small molecule probes currently exist to selectively image Mer. In this work, we design and synthesize a selective near-infrared fluorescent molecular probe of Mer (MERi-SiR). Confocal microscopy of metastases in mice reveals predominant probe accumulation in Mer-expressing tumor-associated macrophages. ...[more]

PMID: 29185561

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Receptor MER Tyrosine Kinase Proto-oncogene (MERTK) Is Not Required for Transfer of Bis-retinoids to the Retinal Pigmented Epithelium.

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Antagonistic Coevolution of MER Tyrosine Kinase Expression and Function.

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Project description:The receptor tyrosine kinase Mer (gene name Mertk) acts in vascular endothelial cells (ECs) to tighten the blood-brain barrier (BBB) subsequent to viral infection. Correspondingly, we found that Mer regulates the expression and activity of a large cohort of cytoskeletal and BBB proteins, together with endothelial nitric oxide synthase, in brain ECs. We further found that Mer controls the expression of multiple angiogenic genes, and that EC-specific Mertk gene inactivation results in perturbed vascular sprouting and a compromised BBB after induced photothrombotic stroke. Unexpectedly, stroke lesions in the brain were also markedly reduced in the absence of EC Mer, which was linked to reduced plasma expression of fibrinogen, prothrombin, and other effectors of blood coagulation. Together, these results demonstrate that Mer is a central regulator of angiogenesis, BBB integrity, and blood coagulation in the mature vasculature. They may also account for disease severity following infection with the coronavirus SARS-CoV-2.

2023-08-24 | GSE225474 | GEO

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