Dataset Information

Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer.

ABSTRACT: Optical biosensing based on the activation of fluorescent reporters offers a powerful methodology for the real-time molecular interrogation of pathology. Here we report a first-in-class, bimodal fluorescent reporter strategy for the simultaneous and highly specific detection of two independent proteases (thrombin and matrix metalloproteases (MMPs)) pivotal in the fibroproliferative process surrounding lung cancer, based on a dual, multiplexing, peptide FRET system. This sophisticated synthetic smartprobe, with a molecular weight of 6 kDa, contains two independent fluorophores and quenchers that generate photonic signatures at two specific wavelengths upon activation by target enzymes within human lung cancer tissue.

SUBMITTER: Megia-Fernandez A

PROVIDER: S-EPMC6238727 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer.

Megia-Fernandez Alicia A Mills Bethany B Michels Chesney C Chankeshwara Sunay V SV Krstajić Nikola N Haslett Chris C Dhaliwal Kevin K Bradley Mark M

Organic & biomolecular chemistry 20181101 43

Optical biosensing based on the activation of fluorescent reporters offers a powerful methodology for the real-time molecular interrogation of pathology. Here we report a first-in-class, bimodal fluorescent reporter strategy for the simultaneous and highly specific detection of two independent proteases (thrombin and matrix metalloproteases (MMPs)) pivotal in the fibroproliferative process surrounding lung cancer, based on a dual, multiplexing, peptide FRET system. This sophisticated synthetic s ...[more]

PMID: 30175355

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Project description:Current paradigms hold that lung carcinomas arise from pleuripotent stem cells capable of differentiation into one or several histological types. These paradigms suggest lung tumor cell ontogeny is determined by consequences of gene expression that recapitulate events important in embryonic lung development. Using oligonucleotide microarrays, we acquired gene profiles from 32 microdissected non-small-cell lung tumors. We determined the 100 top-ranked marker genes for adenocarcinoma, squamous cell, large cell, and carcinoid using nearest neighbor analysis. Results were validated by immunostaining for 11 selected proteins using a tissue microarray representing 80 tumors. Gene expression data of lung development were accessed from a publicly available dataset generated with the murine Mu11k genome microarray. Self-organized mapping identified two temporally distinct clusters of murine orthologues. Supervised clustering of lung development data showed large-cell carcinoma gene orthologues were in a cluster expressed in pseudoglandular and canalicular stages whereas adenocarcinoma homologues were predominantly in a cluster expressed later in the terminal sac and alveolar stages of murine lung development. Representative large-cell genes (E2F3, MYBL2, HDAC2, CDK4, PCNA) are expressed in the nucleus and are associated with cell cycle and proliferation. In contrast, adenocarcinoma genes are associated with lung-specific transcription pathways (SFTPB, TTF-1), cell adhesion, and signal transduction. In sum, non-small-cell lung tumors histology gene profiles suggest mechanisms relevant to ontogeny and clinical course. Adenocarcinoma genes are associated with differentiation and glandular formation whereas large-cell genes are associated with proliferation and differentiation arrest. The identification of developmentally regulated pathways active in tumorigenesis provides insights into lung carcinogenesis and suggests early steps may differ according to the eventual tumor morphology.

Dataset Information

Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer.

Publications

Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer.

Similar Datasets

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