PhD Scientific Days 2020

Pathology and Oncology I. Posters

Metabolic Characteristics of Clear Cell and Papillary Renal Cell Carcinomas

Előadó neve

Dr. Vetlényi, Enikő

Előadó munkahelye

1st Department of Pathology and Experimental Cancer Research

Előadó telefonszáma

+36304169960

Előadó e-mail címe

eniko.vetlenyi@gmail.com

Az előadás címe

Metabolic Characteristics of Clear Cell and Papillary Renal Cell Carcinomas

Szerző(k) neve és munkahelye

E Vetlényi1, I Krencz1, T Dankó1, D Moldvai, G Petővári1, J Pápay1, Gy Végső2, A Sebestyén1
1 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
2 1st Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary

Szekció

Pathology and Oncology I. Posters

Language of the presentation

Hungarian

Section, first choice

Pathology and Oncology

Section, second choice

Clinical Medicine

Összefoglaló szövege

Introduction
Metabolic reprogramming plays an important role in formation and development of kidney cancer. The bioenergetic need of tumor cells could be supported by various metabolic pathways, therefore, clarifying the presence and activity of metabolism-related proteins may provide an opportunity to identify new therapeutic targets.
Aims
Our aim was to characterize the metabolic features of clear renal cell carcinomas (CCRCCs) and papillary renal cell carcinomas (PRCCs) in details using immunohistochemical and in vitro analyses.
Methods
Human tissue samples were collected from patients with CCRCC or PRCC. To assess the expression of mTOR signaling and metabolic markers in CCRCCs and PRCCs, immunohistochemistry was performed using tissue microarray sections. Renal cell carcinoma cell lines (786-O, A498, ACHN) and human kidney proximal tubular epithelial cell line (HK2) were used to analyze the effect of different metabolic inhibitors (rapamycin, BPTES, ACSS2 inhibitor, etomoxir) on tumor growth. The expression of mTOR-related and metabolic enzymes was analyzed by WES Simple technique.
Results
The expressions of GLS, ACSS2, CPT1A (markers for alternative bioenergetic pathways) and ATPB (a marker for oxidative phosphorylation) were significantly higher in PRCCs than in CCRCCs. In contrast, expression of p-S6 (mTORC1 activity marker), GLUT1, and PFKP (glycolytic markers) was higher in CCRCCs. In our in vitro studies, all markers were expressed at a lower level in the HK2 cells as compared to the renal cell carcinoma cell lines. Rapamycin had the highest antiproliferative effect on 786-O cells that had the highest p-S6 expression. 786-O was also sensitive to glutaminase inhibitor, however, those cell lines which express both isoforms of GLS were resistant. ACSS2 inhibitor and etomoxir had a modest effect, however, glutaminase and ACSS2 inhibitors enhanced the antiproliferative effect of rapamycin in some of the cell lines.
Conclusion
In contrast to CCRCCs mTORC1 hyperactivity and high glycolytic marker expressions, PRCCs could use alternative bioenergetic pathways (glutaminolysis, acetate utilization, fatty acid β-oxidation) to fulfill bioenergetic demands. Moreover, our in vitro results suggest potential roles of metabolic inhibitors in renal cell carcinoma treatment.

Additional Information

Anna Sebestyén
E-mail address: hsebanna@gmail.com

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4794

Start

11:29

End

11:32

Authors (legacy)

E Vetlényi1, I Krencz1, T Dankó1, D Moldvai, G Petővári1, J Pápay1, Gy Végső2, A Sebestyén1
1 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
2 1st Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary