Melanoma-derived hyaluronan-coated extracellular vesicles mediate pro-tumorigenic phenotype in macrophages

Melanooma- ja immuunisolujen välinen vuorovaikutus mahdollistaa melanooman kehittymisen pahanlaatuiseksi, sekä metastaasin. Syöpäsoluista peräisin olevat solunulkoiset vesikkelit (extracellular vesicle, EV) pystyvät eriyttämään makrofaageja syövälle edulliseksi fenotyypiksi, mutta tarkat mekanismit...

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Main Author: Korkiamäki, Riku
Other Authors: Matemaattis-luonnontieteellinen tiedekunta, Faculty of Sciences, Bio- ja ympäristötieteiden laitos, Department of Biological and Environmental Science, Jyväskylän yliopisto, University of Jyväskylä
Format: Master's thesis
Language:eng
Published: 2022
Subjects:
Online Access: https://jyx.jyu.fi/handle/123456789/82010
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author Korkiamäki, Riku
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Korkiamäki, Riku Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Korkiamäki, Riku Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Korkiamäki, Riku
datasource_str_mv jyx
description Melanooma- ja immuunisolujen välinen vuorovaikutus mahdollistaa melanooman kehittymisen pahanlaatuiseksi, sekä metastaasin. Syöpäsoluista peräisin olevat solunulkoiset vesikkelit (extracellular vesicle, EV) pystyvät eriyttämään makrofaageja syövälle edulliseksi fenotyypiksi, mutta tarkat mekanismit tälle eivät ole vielä tiedossa. Melanoomasoluissa hyaluronaani syntaasi -geenin ilmentymisen lisääminen lisää hyaluronaanipäällysteisten solunulkoisten vesikkeleiden eritystä. Vesikkeleitä erittyy myös yleisesti paljon syöpäsoluista. Tässä opinnäytetyössä tutkin hyaluronaanipäällysteisten solunulkoisten vesikkeleiden roolia makrofaagien erilaistumisessa. Hyaluronaanipäällysteiset vesikkelit lisäsivät syöpää edistävien sytokiinien ja muiden tekijöiden (IL-1β, IL-8, TSG-6, and PD-L1) ilmentymistä makrofaageissa ja aiheuttivat makrofaageissa pitkänomaista morfologiaa. Erään hyaluronaanin reseptorin, TLR4:n (Toll-like receptor 4), estäminen vähensi sytokiinien eritystä, mikä voi tarkoittaa hyaluronaanipäällysteisten solunulkoisten vesikkeleiden vaikutuksen tapahtuvan TLR4:n kautta. Tutkimuksen tulokset viittaavat uuteen hyaluronaaniin liittyvään mekanismiin, jonka kautta makrofaagit voivat erilaistua syöpää edistäväksi fenotyypiksi. Malignant melanoma development and metastasis is the result of crosstalk between the tumour cells and the immune system. Tumour-derived extracellular vesicles (EVs) can differentiate macrophages into pro-tumorigenic phenotypes. However, the exact molecular mechanisms of EV-mediated macrophage differentiation are still unknown. Hyaluronan synthase (HAS) overexpression increases hyaluronan-coated EV secretion, and EV secretion is a common trait of cancer. Therefore, the differentiation of macrophages could be related to hyaluronan-coated vesicles. To test this hypothesis, macrophages were treated with melanoma-derived hyaluronan-coated vesicles and the expression of cytokines and other factors related in cancer-induced immune modulation were studied. The expression of IL-1β, IL-8, TSG-6, and PD-L1 was elevated in macrophages treated with HAS3 overexpressing melanoma cell-derived EVs (HAS3-MV3 EVs). HAS3-MV3 EVs also induced an elongated morphology in macrophages. Inhibiting TLR4 receptor decreased the cytokine expression induced by HAS3-MV3 EVs, suggesting TLR4-mediated activation. The results suggest a novel hyaluronan-related mechanism for the pro-tumorigenic differentiation of macrophages.
first_indexed 2022-06-23T20:00:31Z
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spellingShingle Korkiamäki, Riku Melanoma-derived hyaluronan-coated extracellular vesicles mediate pro-tumorigenic phenotype in macrophages Solu- ja molekyylibiologia Cell and molecular biology 4013 melanooma makrofagit solunulkoiset vesikkelit immuunijärjestelmä immunologia hyaluronaani tulehdus syöpäsolut melanoma macrophages extracellular vesicles immune system immunology hyaluronan inflammation cancer cells
title Melanoma-derived hyaluronan-coated extracellular vesicles mediate pro-tumorigenic phenotype in macrophages
title_full Melanoma-derived hyaluronan-coated extracellular vesicles mediate pro-tumorigenic phenotype in macrophages
title_fullStr Melanoma-derived hyaluronan-coated extracellular vesicles mediate pro-tumorigenic phenotype in macrophages Melanoma-derived hyaluronan-coated extracellular vesicles mediate pro-tumorigenic phenotype in macrophages
title_full_unstemmed Melanoma-derived hyaluronan-coated extracellular vesicles mediate pro-tumorigenic phenotype in macrophages Melanoma-derived hyaluronan-coated extracellular vesicles mediate pro-tumorigenic phenotype in macrophages
title_short Melanoma-derived hyaluronan-coated extracellular vesicles mediate pro-tumorigenic phenotype in macrophages
title_sort melanoma derived hyaluronan coated extracellular vesicles mediate pro tumorigenic phenotype in macrophages
title_txtP Melanoma-derived hyaluronan-coated extracellular vesicles mediate pro-tumorigenic phenotype in macrophages
topic Solu- ja molekyylibiologia Cell and molecular biology 4013 melanooma makrofagit solunulkoiset vesikkelit immuunijärjestelmä immunologia hyaluronaani tulehdus syöpäsolut melanoma macrophages extracellular vesicles immune system immunology hyaluronan inflammation cancer cells
topic_facet 4013 Cell and molecular biology Solu- ja molekyylibiologia cancer cells extracellular vesicles hyaluronaani hyaluronan immune system immunologia immunology immuunijärjestelmä inflammation macrophages makrofagit melanoma melanooma solunulkoiset vesikkelit syöpäsolut tulehdus
url https://jyx.jyu.fi/handle/123456789/82010 http://www.urn.fi/URN:NBN:fi:jyu-202206233614
work_keys_str_mv AT korkiamäkiriku melanomaderivedhyaluronancoatedextracellularvesiclesmediateprotumorigenicphenotyp