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Illuminating epidermal growth factor receptor densities on filopodia through plasmon coupling.

ABSTRACT: Filopodia have been hypothesized to act as remote sensors of the cell environment, but many details of the sensor function remain unclear. We investigated the distribution of the epidermal growth factor (EGF) receptor (EGFR) density on filopodia and on the dorsal cell membrane of A431 human epidermoid carcinoma cells using a nanoplasmonic enabled imaging tool. We targeted cell surface EGFR with 40 nm diameter Au nanoparticles (NPs) using a high affinity multivalent labeling strategy and determined relative NP binding affinities spatially resolved through plasmon coupling. Distance-dependent near-field interactions between the labels generated a NP density (?)-dependent spectral response that facilitated a spatial mapping of the EGFR density distribution on subcellular length scales in an optical microscope in solution. The measured ? values were significantly higher on filopodia than on the cellular surface, which is indicative of an enrichment of EGFR on filopodia. A detailed characterization of the spatial distribution of the NP immunolabels through scanning electron microscopy (SEM) confirmed the findings of the all-optical plasmon coupling studies and provided additional structural details. The NPs exhibited a preferential association with the sides of the filopodia. We calibrated the ?-dependent spectral response of the Au immunolabels through correlation of optical spectroscopy and SEM. The experimental dependence of the measured plasmon resonance wavelength (?(res)) of the interacting immunolabels on ? was well described by the fit ?(res) = 595.0 nm - 46.36 nm exp(-?/51.48) for ? ? 476 NPs/?m(2). The performed correlated spectroscopic/SEM studies pave the way toward quantitative immunolabeling studies of EGFR and other important cell surface receptors in an optical microscope.

SUBMITTER: Wang J

PROVIDER: S-EPMC3204364 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Illuminating epidermal growth factor receptor densities on filopodia through plasmon coupling.

Wang Jing J Boriskina Svetlana V SV Wang Hongyun H Reinhard Björn M BM

ACS nano 20110722 8

Filopodia have been hypothesized to act as remote sensors of the cell environment, but many details of the sensor function remain unclear. We investigated the distribution of the epidermal growth factor (EGF) receptor (EGFR) density on filopodia and on the dorsal cell membrane of A431 human epidermoid carcinoma cells using a nanoplasmonic enabled imaging tool. We targeted cell surface EGFR with 40 nm diameter Au nanoparticles (NPs) using a high affinity multivalent labeling strategy and determin ...[more]

PMID: 21761914

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Project description:PurposeSubset analyses from phase III evaluation of epidermal growth factor receptor inhibition (EGFRi) suggest improved outcomes in patients with EGFR-amplified gastroesophageal adenocarcinoma (GEA), but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFRi in the largest cohort of patients with EGFR-amplified GEA to date.Patients and methodsA total of 60 patients from 15 tertiary cancer centers in six countries met the inclusion criteria. These criteria required histologically confirmed GEA in the metastatic or unresectable setting with EGFR amplification identified by using a Clinical Laboratory Improvement Amendments-approved assay, and who received on- or off-protocol EGFRi. Testing could be by tissue next-generation sequencing, plasma circulating tumor DNA next-generation sequencing, and/or fluorescence in situ hybridization performed by a Clinical Laboratory Improvement Amendments approved laboratory. Treatment patterns and outcomes analysis was also performed using a deidentified clinicogenomic database (CGDB).ResultsSixty patients with EGFR-amplified GEA received EGFRi, including 31 of 60 patients (52%) with concurrent chemotherapy. Across treatment lines, patients achieved a 43% objective response rate with a median progression-free survival of 4.6 months (95% CI, 3.5 to 6.4). Patients receiving EGFRi in first-, second-, and third-line therapy achieved a median overall survival of 20.6 months (95% CI, 13.5 to not reached [NR]), 9 months (95% CI, 7.9 to NR), and 8.4 months (7.6 to NR), respectively. This survival far exceeded the 11.2-month (95% CI, 8.7 to 14.2) median overall survival from first-line initiation of non-EGFRi therapy in patients with EGFR-amplified GEA in the CGDB. Despite this benefit, analysis of the CGDB (January 2011-December 2020) suggests that only 5% of patients with EGFR-amplified GEA received EGFRi.ConclusionPatients with EGFR-amplified GEA derive significant benefit from EGFRi. Further prospective investigation of EGFRi in a well-selected patient population is ongoing in an upcoming trial of amivantamab in EGFR and/or MET amplified GEA.

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Illuminating epidermal growth factor receptor densities on filopodia through plasmon coupling.

Publications

Illuminating epidermal growth factor receptor densities on filopodia through plasmon coupling.

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