PhD Scientific Days 2021

MO_V_L: Molecular Sciences V. Lectures

The intratumoral heterogeneity of CD44 has the most robust effect on the cargo and release of extracellular vesicles in colorectal cancer

Előadó neve

Ms. Kelemen, Andrea

Előadó munkahelye

Department of Genetics, Cell- and Immunobiology, Molecular Cancer Research Group

Előadó telefonszáma

+36304670714

Előadó e-mail címe

kelemen.andrea93@gmail.com

Az előadás címe

The intratumoral heterogeneity of CD44 has the most robust effect on the cargo and release of extracellular vesicles in colorectal cancer

Szerző(k) neve és munkahelye

Kelemen Andrea1, Idan Carmi1, Wiener Zoltán1

1Semmelweis University, Department of Genetics, Cell and Immunobiology, Molecular Cancer Research Group, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Molecular Sciences V. Lectures

Language of the presentation

English

Preferred session

Molecular Sciences

Összefoglaló szövege

Colorectal cancer (CRC) is one of the most prevalent cancer types. The intra-tumoral heterogeneity is a major feature of CRC, however, its functional importance has not been known yet. CD44, CD133, PTK7 cell surface proteins mark aggressive CRC subpopulations. Extracellular vesicles (EVs) are membrane-surrounded structures released by virtually all cell types and they play a critical role in the intercellular communication. The in vivo cellular heterogeneity of tumors is maintained in the organoids. Here we compared the release intensity and cargo of EVs derived from different CRC subpopulations.
CRC cells from patient-derived organoids were sorted and they were cultured in Matrigel. We analyzed the gene expression pattern of CRC cells with qPCR, flow cytometry, immunohistochemistry. We collected EVs from the supernatant with differential centrifugation. EV number was determined by Nanoparticle Tracking Analysis (NTA). The identity of EVs was proved by transmission electron microscopy and their miRNA cargo was characterized with TaqMan arrays.
The CD44+ and CD133+ populations had only a partial overlap and PTK7+ cells formed a distinct cell population. The diameters of CD44high and CD133high cell-derived organoids were higher compared to organoids from CD44low and CD133low cells, respectively. Interestingly, no difference in organoid size was detected when sorting CRC cells for high and low PTK7 levels. In contrast to PTK7high and CD133high cells that produced similar amount of EVs compared to PTK7low and CD133low cells, we found a markedly higher EV release from CD44high cell-derived organoids than from the CD44low population. In addition, we identified miRNAs specific for the cargo of EVs released by specific CRC cell subpopulations.
We found that whereas CD44+ and CD133+ populations are partially overlapping, PTK7+ cells form a distinct population. The cargo of EVs released by these subpopulations contained specific miRNAs. Our results suggest that the intratumoral cellular heterogeneity characterized by different markers critically determines not only EV release, but EV cargo as well. These data are important when considering EVs as diagnostic tools. This study was supported by BO/00131/20/8 (Hungarian Academy of Sciences), ÚNKP-20-5-SE-18 and by the Richter Gedeon Excellence PhD Scholarship of Richter Gedeon Talentum Foundation.

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine

Supervisor

Dr Zoltán Wiener

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4652

Start

16:30

End

16:45

Authors (legacy)

Kelemen Andrea1, Idan Carmi1, Wiener Zoltán1

1Semmelweis University, Department of Genetics, Cell and Immunobiology, Molecular Cancer Research Group, Budapest, Hungary