PhD Scientific Days 2017

Poster Presentation: Oncology

P44: Metabolic characterisation and mTOR inhibitor induced metabolic alterations in human lymphoma cells

Előadó neve

Nagy, Noémi

Előadó munkahelye

1 1st Department of Pathology and Experimental Cancer Research, Budapest

Előadó telefonszáma

+36 4591500/54430

Előadó e-mail címe

n.noncsi@freemail.hu

Az előadás címe

Metabolic characterisation and mTOR inhibitor induced metabolic alterations in human lymphoma cells

Szerző(k) neve és munkahelye

Noémi Nagy 1, Zoltán Hujber 1, Gábor Petővári 1, Ildikó Krencz 1, Titanilla Dankó 1, Melinda Hajdu 1, Norbert Szoboszlai 2, András Jeney 1, Anna Sebestyén 1,3,
1 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2 Laboratory of Environmental Chemistry and Bioanalytics, Department of Analytical Chemistry, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary
3 Tumour Progression Research Group of Joint Research Organization of Hungarian Academy of Sciences, Semmelweis University, Budapest

Szekció

Poster Presentation: Oncology

Data of the presenter

Supported by: ÚNKP-16-3 (NN), NTP-NFTÖ-16 (ZH) and Bolyai (AS)

Doctoral School: Pathological Science
Program: Experimental Oncology
Program leader: Dr. Anna Sebestyén
E-mail: n.noncsi@freemail.hu
Poster presentation

Text of the abstract

Many data exist about cell- and tissue microenvironmental dependent alteration of immune cell metabolism in context with their differentiation. These changes could be observed in haematological tumour cells, as well. The energy supply of malignant cells is strongly depend on glycolysis, however, this and other bioenergetics processes and their alterations are still poorly characterised in different tumours and lymphomas.
The metabolic activity and its alteration after mTOR inhibitor (rapamycin, NVP-BEZ 235, PP-242) treatments were studied by LC-MS in different lymphoma cells and xenograft models (Hodgkin and Non-Hodgkin lymphoma cell lines – DEV, KMH2, L1236, BHD1). The anti-tumour activity of these treatments were detected by in vitro proliferation assays, flow cytometry and in vivo tumour size measurements. The substrate preference of lymphoma cells was investigated using 13C-labelled glucose, glutamine and acetate. The mTOR activity and substrate utilization related pathways were analysed at protein level, as well.
The studied lymphoma cells showed different mTOR activity with characteristic ratio of mTOR complex proteins (Rictor, Raptor) and mTOR activity related proteins (p-mTOR, p-S6, p-Akt), as well. However, the mTOR inhibitors could reduce the proliferation and the tumour size of lymphomas. The high glycolytic capacity of the studied lymphoma cells were confirmed as we expected. Moreover, both glutamine-, acetate utilization and intact tricarboxylic acid cycle (TCA) capacity were detected in all lymphoma cells. The mTOR inhibitors decreased the expressions of glucose transporter1 and glutaminase in these cells and consequently the glycolytic capacity and the intracellular lactate level were also decreased. Nevertheless, the mTOR inhibitor treatments altered the consumption of other substrates, as well. The acetate consumption and the TCA cycle capacity were induced in some lymphoma cells.
Our results highlight the importance of mTOR activity in metabolic alteration and substrate utilization of lymphoma cells which could influence the therapeutic sensitivity of these and other types of malignant cells.

Azonosító

P44

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1277

Authors (legacy)

Noémi Nagy 1, Zoltán Hujber 1, Gábor Petővári 1, Ildikó Krencz 1, Titanilla Dankó 1, Melinda Hajdu 1, Norbert Szoboszlai 2, András Jeney 1, Anna Sebestyén 1,3,
1 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2 Laboratory of Environmental Chemistry and Bioanalytics, Department of Analytical Chemistry, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary
3 Tumour Progression Research Group of Joint Research Organization of Hungarian Academy of Sciences, Semmelweis University, Budapest