Studies on Multiple Forms of proGRP in Serum from Small Cell Lung Cancer Patients

Nordlund, Marianne S.; Warren, David J.; Laerdahl, Jon K.; Paus, Elisabeth

doi:10.1159/000258135

Cited by 10 publications

(11 citation statements)

References 33 publications

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“…Although these studies had shown decreased neutrophil infiltration within inflamed foci, a possible direct effect of this molecule on neutrophils was not considered until we showed that RC can prevent neutrophil migration in GRP‐induced peritonitis . GRP release in the serum correlates with rheumatoid arthritis , asthma , atopic dermatitis , and cancer . Here, however, although no GRP was found in serum of mice with DILI, treatment with RC impaired neutrophil migration in vivo and in situ.…”

Section: Discussionmentioning

confidence: 76%

GRPR antagonist protects from drug‐induced liver injury by impairing neutrophil chemotaxis and motility

Czepielewski¹,

Jaeger²,

Marques

et al. 2017

Eur J Immunol

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Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF), where hepatocyte necrotic products trigger liver inflammation, release of CXC chemokine receptor 2 (CXCR2) ligands (IL-8) and other neutrophil chemotactic molecules. Liver infiltration by neutrophils is a major cause of the life-threatening tissue damage that ensues. A GRPR (gastrin-releasing peptide receptor) antagonist impairs IL-8-induced neutrophil chemotaxis in vitro. We investigated its potential to reduce acetaminophen-induced ALF, neutrophil migration, and mechanisms underlying this phenomenon. We found that acetaminophen-overdosed mice treated with GRPR antagonist had reduced DILI and neutrophil infiltration in the liver. Intravital imaging and cell tracking analysis revealed reduced neutrophil mobility within the liver. Surprisingly, GRPR antagonist inhibited CXCL2-induced migration in vivo, decreasing neutrophil activation through CD11b and CD62L modulation. Additionally, this compound decreased CXCL8-driven neutrophil chemotaxis in vitro independently of CXCR2 internalization, induced activation of MAPKs (p38 and ERK1/2) and downregulation of neutrophil adhesion molecules CD11b and CD66b. In silico analysis revealed direct binding of GRPR antagonist and CXCL8 to the same binding spot in CXCR2. These findings indicate a new potential use for GRPR antagonist for treatment of DILI through a mechanism involving adhesion molecule modulation and possible direct binding to CXCR2.

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Section: Discussionmentioning

confidence: 76%

GRPR antagonist protects from drug‐induced liver injury by impairing neutrophil chemotaxis and motility

Czepielewski¹,

Jaeger²,

Marques

et al. 2017

Eur J Immunol

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“…The greater stability of the Elecsys® ProGRP assay in serum, relative to the ARCHITECT assay, most likely relates to the antibody-binding sites on the ProGRP peptide. The two monoclonal antibodies in the Elecsys® ProGRP assay bind to epitopes that are relatively resistant to endoproteolytic cleavage [16,17,26], whereas the two monoclonal capture antibodies in the ARCHITECT assay bind directly next to the thrombin-cleavage site (Supplementary Fig. S1).…”

Section: Discussionmentioning

confidence: 99%

“…The Elecsys® ProGRP assay (Roche Diagnostics GmbH, Penzberg, Germany) is a new immunoassay designed to quantitatively determine levels of ProGRP in both human serum and plasma. As the two monoclonal antibodies in the Elecsys® ProGRP assay bind to epitopes in the ProGRP peptide that are relatively resistant to endoproteolytic cleavage [16,17,26] (Supplementary Fig. S1), serum samples as well as plasma samples can be used.…”

Section: Introductionmentioning

confidence: 99%

Multicenter evaluation of a new progastrin-releasing peptide (ProGRP) immunoassay across Europe and China

Korse

Holdenrieder

Zhi

et al. 2015

Clinica Chimica Acta

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“…The idea of investigating expression of the ProGRP isoform in relation to diagnosis and disease was presented earlier. 19 However, to our knowledge, this will be the first report proving the existence of ProGRP isoforms on a protein level. Differentiation between these isoforms could be of clinical value, as well as offering insight into SCLC biology.…”

Section: Introductionmentioning

confidence: 74%

Digging Deeper into the Field of the Small Cell Lung Cancer Tumor Marker ProGRP: A Method for Differentiation of Its Isoforms

et al. 2012

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In this paper, we have used a newly developed immunocapture and LC-MS method to demonstrate for the first time the presence of protein isoforms 1 and 3 of the small cell lung cancer (SCLC) marker progastrin-releasing peptide (ProGRP) in sera. In addition, the method allows for indirect determination of the relative presence of the other known isoform of ProGRP, also known as ProGRP isoform 2. This new method is able to determine total ProGRP as a marker in sera at clinically relevant levels and to differentiate between isoforms at the low-pM level through combining selective sample preparation by immunoextraction, tryptic digestion, and separation followed by detection with LC-SRM-MS of the signature peptides, NLLGLIEAK (total ProGRP), LSAPGSQR (ProGRP isoform 1), and DLVDSLLQVLNVK (ProGRP isoform 3), with accuracies ≤ 25% for lower limit of quantification (LLOQ) and precisions ≤ 33%. By analyzing serum samples from four patients diagnosed with SCLC using the here described new and fully validated method, the ability is shown to both determine total ProGRP concentration and to differentiate between ProGRP isoforms 1 and 3 in one single run. Quantification of various ProGRP isoforms in one single run may be helpful for further understanding of the underlying biochemical processes in SCLC and differentiation of small cell lung cancer.

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Studies on Multiple Forms of proGRP in Serum from Small Cell Lung Cancer Patients

Cited by 10 publications

References 33 publications

GRPR antagonist protects from drug‐induced liver injury by impairing neutrophil chemotaxis and motility

GRPR antagonist protects from drug‐induced liver injury by impairing neutrophil chemotaxis and motility

Multicenter evaluation of a new progastrin-releasing peptide (ProGRP) immunoassay across Europe and China

Digging Deeper into the Field of the Small Cell Lung Cancer Tumor Marker ProGRP: A Method for Differentiation of Its Isoforms

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