Targeting lysyl oxidase for molecular imaging in breast cancer

Introduction Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1–LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. Conclusions The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Wuest, Melinda [verfasserIn] Kuchar, Manuela Sharma, Sai Kiran Richter, Susan Hamann, Ingrit Wang, Monica Vos, Larissa Mackey, John R. Wuest, Frank Löser, Reik

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Breast Cancer Positron Emission Tomography Positron Emission Tomography Radiotracer BAPN Positron Emission Tomography Experiment

Anmerkung:	© Wuest et al. 2015

Übergeordnetes Werk:	Enthalten in: Breast cancer research - London : BioMed Central, 1999, 17(2015), 1 vom: 13. Aug.
Übergeordnetes Werk:	volume:17 ; year:2015 ; number:1 ; day:13 ; month:08

Links:	Volltext

DOI / URN:	10.1186/s13058-015-0609-9

Katalog-ID:	SPR029955521

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520			\|a Introduction Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1–LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. Conclusions The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer.
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allfields	10.1186/s13058-015-0609-9 doi (DE-627)SPR029955521 (SPR)s13058-015-0609-9-e DE-627 ger DE-627 rakwb eng Wuest, Melinda verfasserin aut Targeting lysyl oxidase for molecular imaging in breast cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Wuest et al. 2015 Introduction Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1–LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. Conclusions The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer. Breast Cancer (dpeaa)DE-He213 Positron Emission Tomography (dpeaa)DE-He213 Positron Emission Tomography Radiotracer (dpeaa)DE-He213 BAPN (dpeaa)DE-He213 Positron Emission Tomography Experiment (dpeaa)DE-He213 Kuchar, Manuela aut Sharma, Sai Kiran aut Richter, Susan aut Hamann, Ingrit aut Wang, Monica aut Vos, Larissa aut Mackey, John R. aut Wuest, Frank aut Löser, Reik aut Enthalten in Breast cancer research London : BioMed Central, 1999 17(2015), 1 vom: 13. Aug. (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:17 year:2015 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13058-015-0609-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2015 1 13 08
spelling	10.1186/s13058-015-0609-9 doi (DE-627)SPR029955521 (SPR)s13058-015-0609-9-e DE-627 ger DE-627 rakwb eng Wuest, Melinda verfasserin aut Targeting lysyl oxidase for molecular imaging in breast cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Wuest et al. 2015 Introduction Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1–LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. Conclusions The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer. Breast Cancer (dpeaa)DE-He213 Positron Emission Tomography (dpeaa)DE-He213 Positron Emission Tomography Radiotracer (dpeaa)DE-He213 BAPN (dpeaa)DE-He213 Positron Emission Tomography Experiment (dpeaa)DE-He213 Kuchar, Manuela aut Sharma, Sai Kiran aut Richter, Susan aut Hamann, Ingrit aut Wang, Monica aut Vos, Larissa aut Mackey, John R. aut Wuest, Frank aut Löser, Reik aut Enthalten in Breast cancer research London : BioMed Central, 1999 17(2015), 1 vom: 13. Aug. (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:17 year:2015 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13058-015-0609-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2015 1 13 08
allfields_unstemmed	10.1186/s13058-015-0609-9 doi (DE-627)SPR029955521 (SPR)s13058-015-0609-9-e DE-627 ger DE-627 rakwb eng Wuest, Melinda verfasserin aut Targeting lysyl oxidase for molecular imaging in breast cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Wuest et al. 2015 Introduction Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1–LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. Conclusions The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer. Breast Cancer (dpeaa)DE-He213 Positron Emission Tomography (dpeaa)DE-He213 Positron Emission Tomography Radiotracer (dpeaa)DE-He213 BAPN (dpeaa)DE-He213 Positron Emission Tomography Experiment (dpeaa)DE-He213 Kuchar, Manuela aut Sharma, Sai Kiran aut Richter, Susan aut Hamann, Ingrit aut Wang, Monica aut Vos, Larissa aut Mackey, John R. aut Wuest, Frank aut Löser, Reik aut Enthalten in Breast cancer research London : BioMed Central, 1999 17(2015), 1 vom: 13. Aug. (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:17 year:2015 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13058-015-0609-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2015 1 13 08
allfieldsGer	10.1186/s13058-015-0609-9 doi (DE-627)SPR029955521 (SPR)s13058-015-0609-9-e DE-627 ger DE-627 rakwb eng Wuest, Melinda verfasserin aut Targeting lysyl oxidase for molecular imaging in breast cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Wuest et al. 2015 Introduction Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1–LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. Conclusions The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer. Breast Cancer (dpeaa)DE-He213 Positron Emission Tomography (dpeaa)DE-He213 Positron Emission Tomography Radiotracer (dpeaa)DE-He213 BAPN (dpeaa)DE-He213 Positron Emission Tomography Experiment (dpeaa)DE-He213 Kuchar, Manuela aut Sharma, Sai Kiran aut Richter, Susan aut Hamann, Ingrit aut Wang, Monica aut Vos, Larissa aut Mackey, John R. aut Wuest, Frank aut Löser, Reik aut Enthalten in Breast cancer research London : BioMed Central, 1999 17(2015), 1 vom: 13. Aug. (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:17 year:2015 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13058-015-0609-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2015 1 13 08
allfieldsSound	10.1186/s13058-015-0609-9 doi (DE-627)SPR029955521 (SPR)s13058-015-0609-9-e DE-627 ger DE-627 rakwb eng Wuest, Melinda verfasserin aut Targeting lysyl oxidase for molecular imaging in breast cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Wuest et al. 2015 Introduction Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1–LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. Conclusions The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer. Breast Cancer (dpeaa)DE-He213 Positron Emission Tomography (dpeaa)DE-He213 Positron Emission Tomography Radiotracer (dpeaa)DE-He213 BAPN (dpeaa)DE-He213 Positron Emission Tomography Experiment (dpeaa)DE-He213 Kuchar, Manuela aut Sharma, Sai Kiran aut Richter, Susan aut Hamann, Ingrit aut Wang, Monica aut Vos, Larissa aut Mackey, John R. aut Wuest, Frank aut Löser, Reik aut Enthalten in Breast cancer research London : BioMed Central, 1999 17(2015), 1 vom: 13. Aug. (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:17 year:2015 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13058-015-0609-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2015 1 13 08
language	English
source	Enthalten in Breast cancer research 17(2015), 1 vom: 13. Aug. volume:17 year:2015 number:1 day:13 month:08
sourceStr	Enthalten in Breast cancer research 17(2015), 1 vom: 13. Aug. volume:17 year:2015 number:1 day:13 month:08
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Breast Cancer Positron Emission Tomography Positron Emission Tomography Radiotracer BAPN Positron Emission Tomography Experiment
isfreeaccess_bool	true
container_title	Breast cancer research
authorswithroles_txt_mv	Wuest, Melinda @@aut@@ Kuchar, Manuela @@aut@@ Sharma, Sai Kiran @@aut@@ Richter, Susan @@aut@@ Hamann, Ingrit @@aut@@ Wang, Monica @@aut@@ Vos, Larissa @@aut@@ Mackey, John R. @@aut@@ Wuest, Frank @@aut@@ Löser, Reik @@aut@@
publishDateDaySort_date	2015-08-13T00:00:00Z
hierarchy_top_id	326645950
id	SPR029955521
language_de	englisch
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Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. 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author	Wuest, Melinda
spellingShingle	Wuest, Melinda misc Breast Cancer misc Positron Emission Tomography misc Positron Emission Tomography Radiotracer misc BAPN misc Positron Emission Tomography Experiment Targeting lysyl oxidase for molecular imaging in breast cancer
authorStr	Wuest, Melinda
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topic_title	Targeting lysyl oxidase for molecular imaging in breast cancer Breast Cancer (dpeaa)DE-He213 Positron Emission Tomography (dpeaa)DE-He213 Positron Emission Tomography Radiotracer (dpeaa)DE-He213 BAPN (dpeaa)DE-He213 Positron Emission Tomography Experiment (dpeaa)DE-He213
topic	misc Breast Cancer misc Positron Emission Tomography misc Positron Emission Tomography Radiotracer misc BAPN misc Positron Emission Tomography Experiment
topic_unstemmed	misc Breast Cancer misc Positron Emission Tomography misc Positron Emission Tomography Radiotracer misc BAPN misc Positron Emission Tomography Experiment
topic_browse	misc Breast Cancer misc Positron Emission Tomography misc Positron Emission Tomography Radiotracer misc BAPN misc Positron Emission Tomography Experiment
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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title	Targeting lysyl oxidase for molecular imaging in breast cancer
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title_full	Targeting lysyl oxidase for molecular imaging in breast cancer
author_sort	Wuest, Melinda
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author_browse	Wuest, Melinda Kuchar, Manuela Sharma, Sai Kiran Richter, Susan Hamann, Ingrit Wang, Monica Vos, Larissa Mackey, John R. Wuest, Frank Löser, Reik
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author-letter	Wuest, Melinda
doi_str_mv	10.1186/s13058-015-0609-9
title_sort	targeting lysyl oxidase for molecular imaging in breast cancer
title_auth	Targeting lysyl oxidase for molecular imaging in breast cancer
abstract	Introduction Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1–LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. Conclusions The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer. © Wuest et al. 2015
abstractGer	Introduction Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1–LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. Conclusions The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer. © Wuest et al. 2015
abstract_unstemmed	Introduction Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1–LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. Methods Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 (18F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. Results Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-$ NH_{2} $, was found to be localized in different cellular compartments under these conditions. After injection of [18F]fluorobenzoate-GGGDPKGGGGG-$ NH_{2} $, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. Conclusions The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer. © Wuest et al. 2015
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title_short	Targeting lysyl oxidase for molecular imaging in breast cancer
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author2	Kuchar, Manuela Sharma, Sai Kiran Richter, Susan Hamann, Ingrit Wang, Monica Vos, Larissa Mackey, John R. Wuest, Frank Löser, Reik
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