PhD Scientific Days 2020

Pathology and Oncology I. Posters

Developing Spheroid Models for Mutant KRAS Targeting Strategies

Előadó neve

Baranyi, Marcell, MSc

Előadó munkahelye

Semmelweis University, 2nd Department of Pathology

Előadó telefonszáma

06307337608

Előadó e-mail címe

baranyi2marci@gmail.com

Az előadás címe

Developing Spheroid Models for Mutant KRAS Targeting Strategies

Szerző(k) neve és munkahelye

Marcell Baranyi, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
Eszter Molnár, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
Dominika Rittler, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
Balázs Hegedűs, Department of Thoracic Surgery, Ruhrlandklinik, University Duisburg-Essen, Germany
József Tímár, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary

Szekció

Pathology and Oncology I. Posters

Language of the presentation

Hungarian

Section, first choice

Pathology and Oncology

Section, second choice

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: KRAS is a driver oncogene in a variety of cancer types including adenocarcinomas of the lung, colon and pancreas. However, development of successful targeting strategies is still urgently needed and it requires proper preclinical model systems. One critical aspect is that impact of KRAS mutation seems to be more prominent in 3D enviroments than in 2D cultures.
Aims: We are developing complex tissue like spheroid models containing non-transformed stromal cells that can be used for investigations of KRAS biology and drug development. Additionally, we aim to increase the number of KRAS mutant cell models with spheroid formation capacity by optimizing culture conditions.
Method: Literature based optimization of sphere formation media supplements were performed on SW48 colon cells and isogeneic derivatives transfected with mutant KRAS. Protocol for spheroid processing and embedding was also developed in order to perform histological analysis and immunohistochemistry. Co-cultures of tumor cells with normal fibroblasts and endothelial (HUVEC) cells were treated with a specific covalent inhibitor of KRAS G12C protein.
Results: Sphere formation was successful in all cell lines tested. Immunohistochemical identification of the individual components of the spheroid provide a unique feature to assess specific antitumoral- and bystander drug effects. Based on spheroid size and cell type staining we demonstrated the effective and selective inhibition of tumor cell growth without affecting the stromal cells.
Conclusion: Spheroid cultures of tumor and stromal cells are useful tools for drug development, especially for mutant KRAS targeting. Following optimization, it can be as reproducible and robust as conventional 2D methods.

Additional Information

Supervisor: József Tímár
e-mail adress: timar.jozsef@med.semmelweis-univ.hu

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2709

Start

11:23

End

11:26

Authors (legacy)

Marcell Baranyi, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
Eszter Molnár, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
Dominika Rittler, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
Balázs Hegedűs, Department of Thoracic Surgery, Ruhrlandklinik, University Duisburg-Essen, Germany
József Tímár, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary