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Pancreatic Neoplasms: HELP
Articles by Julie Leca
Based on 5 articles published since 2010
(Why 5 articles?)

Between 2010 and 2020, J. Leca wrote the following 5 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Article LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker. 2018

Bressy, Christian / Lac, Sophie / Nigri, Jérémy / Leca, Julie / Roques, Julie / Lavaut, Marie-Nöelle / Secq, Véronique / Guillaumond, Fabienne / Bui, Thi-Thien / Pietrasz, Daniel / Granjeaud, Samuel / Bachet, Jean-Baptiste / Ouaissi, Mehdi / Iovanna, Juan / Vasseur, Sophie / Tomasini, Richard. ·CRCM, INSERM, U1068; Paoli-Calmettes Institute; Aix-Marseille University, UM 105; CNRS, UMR7258, Marseille, France. · Department of Pathology, Hospital North and Mediterranean University, Marseille, France. · INSERM UMRS 775, University PARIS DESCARTES, Paris, France. · Department of Hepatobiliary and Digestive Surgery, Groupe Hospitalier Pitié Salpêtrière, Paris, France. · Department of Hepatogastroentérology, Groupe Hospitalier Pitié Salpêtrière, Paris, France. · Aix-Marseille University, INSERM, CRO2, UMR 911, Marseille, France. · CRCM, INSERM, U1068; Paoli-Calmettes Institute; Aix-Marseille University, UM 105; CNRS, UMR7258, Marseille, France. richard.tomasini@inserm.fr. ·Cancer Res · Pubmed #29269518.

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.

2 Article Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness. 2016

Leca, Julie / Martinez, Sébastien / Lac, Sophie / Nigri, Jérémy / Secq, Véronique / Rubis, Marion / Bressy, Christian / Sergé, Arnauld / Lavaut, Marie-Noelle / Dusetti, Nelson / Loncle, Céline / Roques, Julie / Pietrasz, Daniel / Bousquet, Corinne / Garcia, Stéphane / Granjeaud, Samuel / Ouaissi, Mehdi / Bachet, Jean Baptiste / Brun, Christine / Iovanna, Juan L / Zimmermann, Pascale / Vasseur, Sophie / Tomasini, Richard. · ·J Clin Invest · Pubmed #27701147.

ABSTRACT: The intratumoral microenvironment, or stroma, is of major importance in the pathobiology of pancreatic ductal adenocarcinoma (PDA), and specific conditions in the stroma may promote increased cancer aggressiveness. We hypothesized that this heterogeneous and evolving compartment drastically influences tumor cell abilities, which in turn influences PDA aggressiveness through crosstalk that is mediated by extracellular vesicles (EVs). Here, we have analyzed the PDA proteomic stromal signature and identified a contribution of the annexin A6/LDL receptor-related protein 1/thrombospondin 1 (ANXA6/LRP1/TSP1) complex in tumor cell crosstalk. Formation of the ANXA6/LRP1/TSP1 complex was restricted to cancer-associated fibroblasts (CAFs) and required physiopathologic culture conditions that improved tumor cell survival and migration. Increased PDA aggressiveness was dependent on tumor cell-mediated uptake of CAF-derived ANXA6+ EVs carrying the ANXA6/LRP1/TSP1 complex. Depletion of ANXA6 in CAFs impaired complex formation and subsequently impaired PDA and metastasis occurrence, while injection of CAF-derived ANXA6+ EVs enhanced tumorigenesis. We found that the presence of ANXA6+ EVs in serum was restricted to PDA patients and represents a potential biomarker for PDA grade. These findings suggest that CAF-tumor cell crosstalk supported by ANXA6+ EVs is predictive of PDA aggressiveness, highlighting a therapeutic target and potential biomarker for PDA.

3 Article TAp73 loss favors Smad-independent TGF-β signaling that drives EMT in pancreatic ductal adenocarcinoma. 2016

Thakur, A K / Nigri, J / Lac, S / Leca, J / Bressy, C / Berthezene, P / Bartholin, L / Chan, P / Calvo, E / Iovanna, J L / Vasseur, S / Guillaumond, F / Tomasini, R. ·CRCM, INSERM, U1068, Paoli-Calmettes Institute, Aix-Marseille University, UM 105; CNRS, UMR7258, Marseille, France. · CRCL, INSERM, U1052; CNRS 5286, Centre Léon Bérard, Lyon, France. · PISSARO Proteomic facility, (IRIB), U-Rouen, Mont Saint- Aignan, France. · Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec, Canada. ·Cell Death Differ · Pubmed #26943320.

ABSTRACT: Advances made in pancreatic cancer therapy have been far from sufficient and have allowed only a slight improvement in global survival of patients with pancreatic ductal adenocarcinoma (PDA). Recent progresses in chemotherapy have offered some hope for an otherwise gloomy outlook, however, only a limited number of patients are eligible because of important cytotoxicity. In this context, enhancing our knowledge on PDA initiation and evolution is crucial to highlight certain weaknesses on which to specifically target therapy. We found that loss of transcriptionally active p73 (TAp73), a p53 family member, impacted PDA development. In two relevant and specific engineered pancreatic cancer mouse models, we observed that TAp73 deficiency reduced survival and enhanced epithelial-to-mesenchymal transition (EMT). Through proteomic analysis of conditioned media from TAp73 wild-type (WT) and deficient pancreatic tumor cells, we identified a secreted protein, biglycan (BGN), which is necessary and sufficient to mediate this pro-EMT effect. Interestingly, BGN is modulated by and modulates the transforming growth factor-β (TGF-β) pathway, a key regulator of the EMT process. We further examined this link and revealed that TAp73 impacts the TGF-β pathway by direct regulation of BGN expression and Sma and Mad-related proteins (SMADs) expression/activity. Absence of TAp73 leads to activation of TGF-β signaling through a SMAD-independent pathway, favoring oncogenic TGF-β effects and EMT. Altogether, our data highlight the implication of TAp73 in the aggressiveness of pancreatic carcinogenesis through modulation of the TGF-β signaling. By suggesting TAp73 as a predictive marker for response to TGF-β inhibitors, our study could improve the classification of PDA patients with a view to offering combined therapy involving TGF-β inhibitors.

4 Article Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling. 2015

Secq, V / Leca, J / Bressy, C / Guillaumond, F / Skrobuk, P / Nigri, J / Lac, S / Lavaut, M-N / Bui, T-T / Thakur, A K / Callizot, N / Steinschneider, R / Berthezene, P / Dusetti, N / Ouaissi, M / Moutardier, V / Calvo, E / Bousquet, C / Garcia, S / Bidaut, G / Vasseur, S / Iovanna, J L / Tomasini, R. ·1] CRCM, Cellular Stress, INSERM, U1068, Parc scientifique de Luminy, Paoli-Calmettes Institute, Aix-Marseille University, UM 105, CNRS, UMR7258, Marseille 13009, France [2] Department of Pathology, Hospital North/Mediterranean University, Marseille, France. · CRCM, Cellular Stress, INSERM, U1068, Parc scientifique de Luminy, Paoli-Calmettes Institute, Aix-Marseille University, UM 105, CNRS, UMR7258, Marseille 13009, France. · Neuronexperts, Medical North Faculty, Marseille, France. · Aix-Marseille University, INSERM, CRO2, UMR 911, Marseille 13385, France. · Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec City, QCue, Canada. · INSERM UMR 1037, CRCT, University Toulouse III, Toulouse, France. ·Cell Death Dis · Pubmed #25590802.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is a critical health issue in the field of cancer, with few therapeutic options. Evidence supports an implication of the intratumoral microenvironment (stroma) on PDA progression. However, its contribution to the role of neuroplastic changes within the pathophysiology and clinical course of PDA, through tumor recurrence and neuropathic pain, remains unknown, neglecting a putative, therapeutic window. Here, we report that the intratumoral microenvironment is a mediator of PDA-associated neural remodeling (PANR), and we highlight factors such as 'SLIT2' (an axon guidance molecule), which is expressed by cancer-associated fibroblasts (CAFs), that impact on neuroplastic changes in human PDA. We showed that 'CAF-secreted SLIT2' increases neurite outgrowth from dorsal root ganglia neurons as well as from Schwann cell migration/proliferation by modulating N-cadherin/β-catenin signaling. Importantly, SLIT2/ROBO signaling inhibition disrupts this stromal/neural connection. Finally, we revealed that SLIT2 expression and CAFs are correlated with neural remodeling within human and mouse PDA. All together, our data demonstrate the implication of CAFs, through the secretion of axon guidance molecule, in PANR. Furthermore, it provides rationale to investigate the disruption of the stromal/neural compartment connection with SLIT2/ROBO inhibitors for the treatment of pancreatic cancer recurrence and pain.

5 Article Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. 2013

Guillaumond, Fabienne / Leca, Julie / Olivares, Orianne / Lavaut, Marie-Noëlle / Vidal, Nicolas / Berthezène, Patrice / Dusetti, Nelson Javier / Loncle, Céline / Calvo, Ezequiel / Turrini, Olivier / Iovanna, Juan Lucio / Tomasini, Richard / Vasseur, Sophie. ·Centre de Recherche en Cancérologie de Marseille (CRCM), Unité 1068, Institut National de la Santé et de la Recherche Médicale, F-13009 Marseille, France. ·Proc Natl Acad Sci U S A · Pubmed #23407165.

ABSTRACT: Pancreatic ductal adenocarcinoma is one of the most intractable and fatal cancer. The decreased blood vessel density displayed by this tumor not only favors its resistance to chemotherapy but also participates in its aggressiveness due to the consequent high degree of hypoxia. It is indeed clear that hypoxia promotes selective pressure on malignant cells that must develop adaptive metabolic responses to reach their energetic and biosynthetic demands. Here, using a well-defined mouse model of pancreatic cancer, we report that hypoxic areas from pancreatic ductal adenocarcinoma are mainly composed of epithelial cells harboring epithelial-mesenchymal transition features and expressing glycolytic markers, two characteristics associated with tumor aggressiveness. We also show that hypoxia increases the "glycolytic" switch of pancreatic cancer cells from oxydative phosphorylation to lactate production and we demonstrate that increased lactate efflux from hypoxic cancer cells favors the growth of normoxic cancer cells. In addition, we show that glutamine metabolization by hypoxic pancreatic tumor cells is necessary for their survival. Metabolized glucose and glutamine converge toward a common pathway, termed hexosamine biosynthetic pathway, which allows O-linked N-acetylglucosamine modifications of proteins. Here, we report that hypoxia increases transcription of hexosamine biosynthetic pathway genes as well as levels of O-glycosylated proteins and that O-linked N-acetylglucosaminylation of proteins is a process required for hypoxic pancreatic cancer cell survival. Our results demonstrate that hypoxia-driven metabolic adaptive processes, such as high glycolytic rate and hexosamine biosynthetic pathway activation, favor hypoxic and normoxic cancer cell survival and correlate with pancreatic ductal adenocarcinoma aggressiveness.