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B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent stromal reaction that has been variably implicated in both tumor growth and tumor suppression. B-lymphocytes have been recently implicated in PDAC progression but their contribution to the characteristic stromal desmoplasia has...

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Autores principales: Minici, Claudia, Rigamonti, Elena, Lanzillotta, Marco, Monno, Antonella, Rovati, Lucrezia, Maehara, Takashi, Kaneko, Naoki, Deshpande, Vikram, Protti, Maria Pia, De Monte, Lucia, Scielzo, Cristina, Crippa, Stefano, Arcidiacono, Paolo Giorgio, Dugnani, Erica, Piemonti, Lorenzo, Falconi, Massimo, Pillai, Shiv, Manfredi, Angelo A., Della-Torre, Emanuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458626/
https://www.ncbi.nlm.nih.gov/pubmed/32923157
http://dx.doi.org/10.1080/2162402X.2020.1794359
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author Minici, Claudia
Rigamonti, Elena
Lanzillotta, Marco
Monno, Antonella
Rovati, Lucrezia
Maehara, Takashi
Kaneko, Naoki
Deshpande, Vikram
Protti, Maria Pia
De Monte, Lucia
Scielzo, Cristina
Crippa, Stefano
Arcidiacono, Paolo Giorgio
Dugnani, Erica
Piemonti, Lorenzo
Falconi, Massimo
Pillai, Shiv
Manfredi, Angelo A.
Della-Torre, Emanuel
author_facet Minici, Claudia
Rigamonti, Elena
Lanzillotta, Marco
Monno, Antonella
Rovati, Lucrezia
Maehara, Takashi
Kaneko, Naoki
Deshpande, Vikram
Protti, Maria Pia
De Monte, Lucia
Scielzo, Cristina
Crippa, Stefano
Arcidiacono, Paolo Giorgio
Dugnani, Erica
Piemonti, Lorenzo
Falconi, Massimo
Pillai, Shiv
Manfredi, Angelo A.
Della-Torre, Emanuel
author_sort Minici, Claudia
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent stromal reaction that has been variably implicated in both tumor growth and tumor suppression. B-lymphocytes have been recently implicated in PDAC progression but their contribution to the characteristic stromal desmoplasia has never been assessed before. In the present work, we aimed to verify whether B-lymphocytes contribute to stromal cell activation in PDAC. CD19(+) B-lymphocytes purified from peripheral blood of patients with PDAC were cultivated in the presence of human pancreatic fibroblasts and cancer-associated fibroblasts. Released pro-fibrotic soluble factors and collagen production were assessed by ELISA and Luminex assays. Quantitative RT-PCR was used to assess fibroblast activation in the presence of B cells. The expression of selected pro-fibrotic and inflammatory molecules was confirmed on PDAC tissue sections by multi-color immunofluorescence studies. We herein demonstrate that B-cells from PDAC patients (i) produce the pro-fibrotic molecule PDGF-B and stimulate collagen production by fibroblasts; (ii) express enzymes implicated in extracellular matrix remodeling including LOXL2; and (iii) produce the chemotactic factors CCL-4, CCL-5, and CCL-11. In addition we demonstrate that circulating plasmablasts are expanded in the peripheral blood of patients with PDAC, stimulate collagen production by fibroblasts, and infiltrate pancreatic lesions. Our results indicate that PDAC is characterized by perturbations of the B-cell compartment with expansion of B-lymphocyte subsets that directly contribute to the stromal reaction observed at disease site. These findings provide an additional rationale for modulating B-cell activity in patients with pancreatic cancer.
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spelling pubmed-74586262020-09-11 B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma Minici, Claudia Rigamonti, Elena Lanzillotta, Marco Monno, Antonella Rovati, Lucrezia Maehara, Takashi Kaneko, Naoki Deshpande, Vikram Protti, Maria Pia De Monte, Lucia Scielzo, Cristina Crippa, Stefano Arcidiacono, Paolo Giorgio Dugnani, Erica Piemonti, Lorenzo Falconi, Massimo Pillai, Shiv Manfredi, Angelo A. Della-Torre, Emanuel Oncoimmunology Original Research Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent stromal reaction that has been variably implicated in both tumor growth and tumor suppression. B-lymphocytes have been recently implicated in PDAC progression but their contribution to the characteristic stromal desmoplasia has never been assessed before. In the present work, we aimed to verify whether B-lymphocytes contribute to stromal cell activation in PDAC. CD19(+) B-lymphocytes purified from peripheral blood of patients with PDAC were cultivated in the presence of human pancreatic fibroblasts and cancer-associated fibroblasts. Released pro-fibrotic soluble factors and collagen production were assessed by ELISA and Luminex assays. Quantitative RT-PCR was used to assess fibroblast activation in the presence of B cells. The expression of selected pro-fibrotic and inflammatory molecules was confirmed on PDAC tissue sections by multi-color immunofluorescence studies. We herein demonstrate that B-cells from PDAC patients (i) produce the pro-fibrotic molecule PDGF-B and stimulate collagen production by fibroblasts; (ii) express enzymes implicated in extracellular matrix remodeling including LOXL2; and (iii) produce the chemotactic factors CCL-4, CCL-5, and CCL-11. In addition we demonstrate that circulating plasmablasts are expanded in the peripheral blood of patients with PDAC, stimulate collagen production by fibroblasts, and infiltrate pancreatic lesions. Our results indicate that PDAC is characterized by perturbations of the B-cell compartment with expansion of B-lymphocyte subsets that directly contribute to the stromal reaction observed at disease site. These findings provide an additional rationale for modulating B-cell activity in patients with pancreatic cancer. Taylor & Francis 2020-07-16 /pmc/articles/PMC7458626/ /pubmed/32923157 http://dx.doi.org/10.1080/2162402X.2020.1794359 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Minici, Claudia
Rigamonti, Elena
Lanzillotta, Marco
Monno, Antonella
Rovati, Lucrezia
Maehara, Takashi
Kaneko, Naoki
Deshpande, Vikram
Protti, Maria Pia
De Monte, Lucia
Scielzo, Cristina
Crippa, Stefano
Arcidiacono, Paolo Giorgio
Dugnani, Erica
Piemonti, Lorenzo
Falconi, Massimo
Pillai, Shiv
Manfredi, Angelo A.
Della-Torre, Emanuel
B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma
title B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma
title_full B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma
title_fullStr B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma
title_full_unstemmed B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma
title_short B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma
title_sort b lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458626/
https://www.ncbi.nlm.nih.gov/pubmed/32923157
http://dx.doi.org/10.1080/2162402X.2020.1794359
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