Oncotarget

Research Papers:

Characterization of increasing stages of invasiveness identifies stromal/cancer cell crosstalk in rat models of mesothelioma

Joëlle S. Nader, Jérôme Abadie, Sophie Deshayes, Alice Boissard, Stéphanie Blandin, Christophe Blanquart, Nicolas Boisgerault, Olivier Coqueret, Catherine Guette, Marc Grégoire and Daniel L. Pouliquen _

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Oncotarget. 2018; 9:16311-16329. https://doi.org/10.18632/oncotarget.24632

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Abstract

Joëlle S. Nader1, Jérôme Abadie1,2, Sophie Deshayes1, Alice Boissard3,4, Stéphanie Blandin5, Christophe Blanquart1, Nicolas Boisgerault1, Olivier Coqueret3,4, Catherine Guette3,4, Marc Grégoire1 and Daniel L. Pouliquen1

1CRCINA, INSERM, Université d’Angers, Université de Nantes, Nantes, France

2ONIRIS, Nantes, France

3CRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France

4ICO, Angers, France

5Plate-Forme MicroPICell, SFR François Bonamy, Université de Nantes, France

Correspondence to:

Daniel L. Pouliquen, email: daniel.pouliquen@inserm.fr

Keywords: stroma; invasiveness; sarcomatoid mesothelioma; immune cells; rat model

Received: November 08, 2017     Accepted: February 25, 2018     Published: March 27, 2018

ABSTRACT

Sarcomatoid mesothelioma (SM) is a devastating cancer associated with one of the poorest outcome. Therefore, representative preclinical models reproducing different tumor microenvironments (TME) observed in patients would open up new prospects for the identification of markers and evaluation of innovative therapies. Histological analyses of four original models of rat SM revealed their increasing infiltrative and metastatic potential were associated with differences in Ki67 index, blood-vessel density, and T-lymphocyte and macrophage infiltration. In comparison with the noninvasive tumor M5-T2, proteomic analysis demonstrated the three invasive tumors F4-T2, F5-T1 and M5-T1 shared in common a very significant increase in the abundance of the multifunctional proteins galectin-3, prohibitin and annexin A5, and a decrease in proteins involved in cell adhesion, tumor suppression, or epithelial differentiation. The increased metastatic potential of the F5-T1 tumor, relative to F4-T2, was associated with an increased macrophage vs T-cell infiltrate, changes in the levels of expression of a panel of cytokine genes, an increased content of proteins involved in chromatin organization, ribosome structure, splicing, or presenting anti-adhesive properties, and a decreased content of proteins involved in protection against oxidative stress, normoxia and intracellular trafficking. The most invasive tumor, M5-T1, was characterized by a pattern of specific phenotypic and molecular features affecting the presentation of MHC class I-mediated antigens and immune cell infiltration, or involved in the reorganization of the cytoskeleton and composition of the extracellular matrix. These four preclinical models and data represent a new resource available to the cancer research community to catalyze further investigations on invasiveness.


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