American Association for Cancer Research
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Figure S3 from LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker

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posted on 2023-03-31, 00:09 authored by Christian Bressy, Sophie Lac, Jérémy Nigri, Julie Leca, Julie Roques, Marie-Nöelle Lavaut, Véronique Secq, Fabienne Guillaumond, Thi-Thien Bui, Daniel Pietrasz, Samuel Granjeaud, Jean-Baptiste Bachet, Mehdi Ouaissi, Juan Iovanna, Sophie Vasseur, Richard Tomasini

Amalysis of Akt/Stat3 signaling induction following LIF stimulation. We measured the induction of STAT3 (A) and Akt (B) phosphorylation by western blot in sNF96.2 after incubation with LIF recombinant protein. We confirmed the specificity of induction triggered by LIF using LIFR blocking antibody or AG490 inhibitor.

Funding

ARC

INCa

European Union Seventh Framework Programme

INSERM

Aix-Marseille University

Fondation pour la Recherche Médicale

European Research Council

History

ARTICLE ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive stroma and pathogenic modifications to the peripheral nervous system that elevate metastatic capacity. In this study, we show that the IL6-related stem cell–promoting factor LIF supports PDAC-associated neural remodeling (PANR). LIF was overexpressed in tumor tissue compared with healthy pancreas, but its receptors LIFR and gp130 were expressed only in intratumoral nerves. Cancer cells and stromal cells in PDAC tissues both expressed LIF, but only stromal cells could secrete it. Biological investigations showed that LIF promoted the differentiation of glial nerve sheath Schwann cells and induced their migration by activating JAK/STAT3/AKT signaling. LIF also induced neuronal plasticity in dorsal root ganglia neurons by increasing the number of neurites and the soma area. Notably, injection of LIF-blocking antibody into PDAC-bearing mice reduced intratumoral nerve density, supporting a critical role for LIF function in PANR. In serum from human PDAC patients and mouse models of PDAC, we found that LIF titers positively correlated with intratumoral nerve density. Taken together, our findings suggest LIF as a candidate serum biomarker and diagnostic tool and a possible therapeutic target for limiting the impact of PANR in PDAC pathophysiology and metastatic progression.Significance: This study suggests a target to limit neural remodeling in pancreatic cancer, which contributes to poorer quality of life and heightened metastatic progression in patients. Cancer Res; 78(4); 909–21. ©2017 AACR.