Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells. The increased glutamine uptake was paralleled by higher activity of most glutamine pathway-related enzymes supporting nucleotide and ATP production. Free glutamine blood levels were evaluated in orthotopic and spontaneous mouse models of PDAC and other pancreatic-related disorders by High-Performance Liquid Chromatography (HPLC) and/or MS. Notably we observed a reduction of blood glutamine as much as the tumor progressed from pancreatic intraepithelial lesions to invasive PDAC, but was not related to chronic pancreatitis-associated inflammation or diabetes. In parallel the increased levels of branched-chain amino acids (BCAA) were observed. By contrast blood glutamine levels were stable in non-tumor bearing mice. These findings demonstrated that glutamine uptake is measurable both in vitro and in vivo. The higher in vitro avidity of PDAC cells corresponded to a lower blood glutamine level as soon as the tumor mass grew. The reduction in circulating glutamine represents a novel tool exploitable to implement other diagnostic or prognostic PDAC biomarkers.

Endogenous glutamine decrease is associated with pancreatic cancer progression

Roux, Cecilia;Riganti, Chiara;Borgogno, Sammy Ferri;CURTO, ROBERTA;Curcio, Claudia;Catanzaro, Valeria;Digilio, Giuseppe;Aime, Silvio;Cappello, Paola
Co-last
;
Novelli, Francesco
2017

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells. The increased glutamine uptake was paralleled by higher activity of most glutamine pathway-related enzymes supporting nucleotide and ATP production. Free glutamine blood levels were evaluated in orthotopic and spontaneous mouse models of PDAC and other pancreatic-related disorders by High-Performance Liquid Chromatography (HPLC) and/or MS. Notably we observed a reduction of blood glutamine as much as the tumor progressed from pancreatic intraepithelial lesions to invasive PDAC, but was not related to chronic pancreatitis-associated inflammation or diabetes. In parallel the increased levels of branched-chain amino acids (BCAA) were observed. By contrast blood glutamine levels were stable in non-tumor bearing mice. These findings demonstrated that glutamine uptake is measurable both in vitro and in vivo. The higher in vitro avidity of PDAC cells corresponded to a lower blood glutamine level as soon as the tumor mass grew. The reduction in circulating glutamine represents a novel tool exploitable to implement other diagnostic or prognostic PDAC biomarkers.
8
56
95361
95376
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=20545&path%5B%5D=65491
Amino acid; Circulating biomarkers; Diagnosis; Pancreatitis; PDAC;
Roux C.; Riganti C.; Borgogno S.F.; Curto R.; Curcio C.; Catanzaro V.; Digilio G.; Padovan S.; Puccinelli M.P.; Isabello M.; Aime S.; Cappello P.; Novelli F.
File in questo prodotto:
File Dimensione Formato  
Roux, MS and Supporting, Oncotarget 2017.pdf

Accesso aperto

Descrizione: Roux, Oncotarget Open Access 2017
Tipo di file: PDF EDITORIALE
Dimensione 6.63 MB
Formato Adobe PDF
6.63 MB Adobe PDF Visualizza/Apri
Roux, MS and Supporting, Oncotarget 2017.pdf

Accesso riservato

Descrizione: Roux, Oncotarget manuscript and Supporting, 2017
Tipo di file: PDF EDITORIALE
Dimensione 6.63 MB
Formato Adobe PDF
6.63 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1656374
Citazioni
  • ???jsp.display-item.citation.pmc??? 16
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 25
social impact