Chitinase 3-like-1 and fibronectin in the cargo of extracellular vesicles shed by human macrophages influence pancreatic cancer cellular response to gemcitabine

• Tipo: Artigo em Revista Científica Internacional
• Data: 2021

Autores

Xavier, CPR (Autor) Outra; Castro, I (Autor) Outra; Caires, HR (Autor) Outra; Ferreira, D (Autor) Outra; Cavadas, B (Autor) Outra; Pereira, L (Autor) Outra; Santos, LL (Autor) Outra; Oliveira, MJ (Autor) ICBAS; Helena Vasconcelos, MH (Autor) FFUP

Revista

Título: Cancer Letters

Vol. 501

Páginas: 210-223

ISSN: 0304-3835

Editora: Elsevier

Indexação

ISI Web of Knowledge - 29 Citações

Scopus - 28 Citações

Outras Informações

ID Authenticus: P-00T-3ZS

DOI: 10.1016/j.canlet.2020.11.013

Abstract (EN): Tumour-associated macrophages have been implicated in pancreatic ductal adenocarcinoma (PDAC) therapy response and Extracellular vesicles (EVs) shed by macrophages might have a role in this process. Here, we demonstrated that large EVs released by anti-inflammatory human macrophages decreased PDAC cellular sensitivity to gemcitabine. Using proteomic analysis, chitinase 3-like-1 (CHI3L1) and fibronectin (FN1) were identified as two of the most abundant proteins in the cargo of macrophages-derived EVs. Overexpression of CHI3L1 and FN1, using recombinant human proteins, induced PDAC cellular resistance to gemcitabine through ERK (extracellular-signal-regulated kinase) activation. Inhibition of CHI3L1 and FN1 by pentoxifylline and pirfenidone, respectively, partially reverted gemcitabine resistance. In PDAC patient samples, CHI3L1 and FN1 were expressed in the stmma, associated with the high presence of macrophages. The Cancer Genome Atlas analysis revealed an association between CHI3L1 and FNI gene expression, overall survival of PDAC patients, gemcitabine response, and macrophage infiltration. Altogether, our data identifies CHI3L1 and FN1 as potential targets for pharmacological inhibition in PDAC. Further pre-clinical in vivo work is warranted to study the possibility of repurposing pentoxifylline and pirfenidone as adjuvant therapies for PDAC treatment.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14