Extracellular vesicle release from intestinal organoids is modulated by Apc mutation and other colorectal cancer progression factors

Zsuzsanna Szvicsek, Ádám Oszvald, Lili Szabó, Gyöngyvér Orsolya Sándor, Andrea Kelemen, András Áron Soós, Krisztina Pálóczi, László Harsányi, Tamás Tölgyes, Kristóf Dede, Attila Bursics, E. Búzás, A. Zeöld, Zoltán Wiener

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Extracellular vesicles (EVs) are membrane-surrounded structures that transmit biologically important molecules from the releasing to target cells, thus providing a novel intercellular communication mechanism. Since EVs carry their cargo in a protected form and their secretion is generally increased in tumorigenesis, EVs hold a great potential for early cancer diagnosis. By 3D culturing, we provide evidence that colorectal cancer (CRC) patient-derived organoids, representing a state-of-the-art established and essential approach for studying human CRC, is a suitable model for EV analysis. When testing the effects of major factors promoting CRC progression on EV release in the organoid model, we observed that Apc mutation, leading to uncontrolled Wnt activation and thus to tumorigenesis in the vast majority in CRC patients, critically induces EV release by activating the Wnt pathway. Furthermore, the extracellular matrix component collagen, known to accumulate in tumorigenesis, enhances EV secretion as well. Importantly, we show that fibroblast-derived EVs induce colony formation of CRC organoid cells under hypoxia. In contrast, there was no major effect of tumor cell-derived EVs on the activation of fibroblasts. Collectively, our results with CRC and Apc-mutant adenoma organoids identify Apc mutation and collagen deposition as critical factors for increasing EV release from tumors. Furthermore, we provide evidence that stromal fibroblast-derived EVs contribute to tumorigenesis under unfavorable conditions in CRC.

Original languageEnglish
JournalCellular and Molecular Life Sciences
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Organoids
Colorectal Neoplasms
Mutation
Carcinogenesis
Fibroblasts
Extracellular Vesicles
Collagen
Cell Hypoxia
Wnt Signaling Pathway
Early Detection of Cancer
Adenoma
Extracellular Matrix
Neoplasms

Keywords

  • Adenoma
  • Cancer patient-derived organoid
  • Collagen
  • Exosome
  • Stroma
  • Tumor

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Extracellular vesicle release from intestinal organoids is modulated by Apc mutation and other colorectal cancer progression factors. / Szvicsek, Zsuzsanna; Oszvald, Ádám; Szabó, Lili; Sándor, Gyöngyvér Orsolya; Kelemen, Andrea; Soós, András Áron; Pálóczi, Krisztina; Harsányi, László; Tölgyes, Tamás; Dede, Kristóf; Bursics, Attila; Búzás, E.; Zeöld, A.; Wiener, Zoltán.

In: Cellular and Molecular Life Sciences, 01.01.2019.

Research output: Contribution to journalArticle

Szvicsek, Z, Oszvald, Á, Szabó, L, Sándor, GO, Kelemen, A, Soós, AÁ, Pálóczi, K, Harsányi, L, Tölgyes, T, Dede, K, Bursics, A, Búzás, E, Zeöld, A & Wiener, Z 2019, 'Extracellular vesicle release from intestinal organoids is modulated by Apc mutation and other colorectal cancer progression factors', Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-019-03052-1
Szvicsek, Zsuzsanna ; Oszvald, Ádám ; Szabó, Lili ; Sándor, Gyöngyvér Orsolya ; Kelemen, Andrea ; Soós, András Áron ; Pálóczi, Krisztina ; Harsányi, László ; Tölgyes, Tamás ; Dede, Kristóf ; Bursics, Attila ; Búzás, E. ; Zeöld, A. ; Wiener, Zoltán. / Extracellular vesicle release from intestinal organoids is modulated by Apc mutation and other colorectal cancer progression factors. In: Cellular and Molecular Life Sciences. 2019.
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AU - Oszvald, Ádám

AU - Szabó, Lili

AU - Sándor, Gyöngyvér Orsolya

AU - Kelemen, Andrea

AU - Soós, András Áron

AU - Pálóczi, Krisztina

AU - Harsányi, László

AU - Tölgyes, Tamás

AU - Dede, Kristóf

AU - Bursics, Attila

AU - Búzás, E.

AU - Zeöld, A.

AU - Wiener, Zoltán

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