PhD Scientific Days 2020

Molecular Sciences IV. Lectures

The Effect of TGF-β on the Extracellular Vesicle Production of Normal Colon and Colorectal Cancer Fibroblasts

Előadó neve

Szvicsek, Zsuzsanna, MSc

Előadó munkahelye

Semmelweis University, Department of Genetics, Cell - and Immunobiology

Előadó telefonszáma

+36704241393

Előadó e-mail címe

zsuzsanna.szvicsek@gmx.com

Az előadás címe

The Effect of TGF-β on the Extracellular Vesicle Production of Normal Colon and Colorectal Cancer Fibroblasts

Szerző(k) neve és munkahelye

Szvicsek, Zs., 2Pápai, M., 2Wiener Z.

1 Szvicsek, Zs., Semmelweis University, Department of Genetics, Cell and Immunobiology, Molecular Cancer Research Group, Budapest, Hungary
2 Pápai, M., Semmelweis University, Department of Genetics, Cell and Immunobiology, Molecular Cancer Research Group, Budapest, Hungary
3 Wiener Z. Semmelweis University, Department of Genetics, Cell and Immunobiology, Molecular Cancer Research Group, Budapest, Hungary

Szekció

Molecular Sciences IV. Lectures

Language of the presentation

Hungarian

Section, first choice

Molecular Sciences

Section, second choice

Pathology and Oncology

Összefoglaló szövege

Colorectal cancer (CRC) is one of the most frequent causes of cancer-related death. The tumor microenvironment contains not only cancer cells, but other cell types, such as cancer associated fibroblasts (CAF) as well. TGFβ is a critical factor that activate stromal fibroblasts and induces invasion and metastasis in CRC. Importantly, peritumoral fibroblasts (PTF) are often used as normal colon fibroblasts. The high amount of CAFs in CRC is strongly correlated with a poor clinical outcome. Extracellular vesicles (EVs) are membrane-surrounded structures that represent a novel way of intercellular communication by delivering biologically important molecules from the releasing to the target cells. Since EVs carry their cargo in a protected and concentrated form, furthermore, their secretion is generally increased in tumorigenesis, EVs hold a great potential for early cancer diagnosis. Here we study factors influencing stromal fibroblast-derived EV production intensity and cargo composition as a transmitting tool in CRC.
We used patient-derived organoids and fibroblasts, furthermore, commercial available normal colon fibroblasts (NCF). The Medical Research Council of Hungary approved our experiments and informed consent was obtained from patients. EVs were detected by antibody-coated beads and flow cytometry and by Nanoparticle Tracking Analysis. Gene expression was followed by RT-qPCR and immunocytochemistry. For miRNA detection we used the TaqMan system.
We provide evidence that EVs can be detected in patient-derived normal colon fibroblast (PTF) and cancer associated fibroblast (CAF) cultures by a simple semi-quantitative flow cytometry-based method. We show that TGF-β, an important activator of fibroblasts, enhances EV secretion of NCFs, PTFs and CAFs. In addition, TGFβ modifies the miRNA cargo of EVs in fibroblasts. Interestingly, TGF-β treatment lead to the emergence of IL6+ fibroblast subpopulations both in PTF and CAF, but not in NCF cultures. Collectively, our results show that TGF-β, a critical factor modifying fibroblast functions, has a major effect on EV release and cargo.

This work was funded by OTKA-NN 118018 and by the ÚNKP-19-3-I-SE-62 New National Excellence Program of the Ministry for Innovation and Technology (Zs.Sz.).

Additional Information

Supervisor: Zoltán Wiener
wiener.zoltan@med.semmelweis-univ.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4671

Start

12:10

End

12:25

Authors (legacy)

Szvicsek, Zs., 2Pápai, M., 2Wiener Z.

1 Szvicsek, Zs., Semmelweis University, Department of Genetics, Cell and Immunobiology, Molecular Cancer Research Group, Budapest, Hungary
2 Pápai, M., Semmelweis University, Department of Genetics, Cell and Immunobiology, Molecular Cancer Research Group, Budapest, Hungary
3 Wiener Z. Semmelweis University, Department of Genetics, Cell and Immunobiology, Molecular Cancer Research Group, Budapest, Hungary