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Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells

BACKGROUND: Tumour cells release membrane micro(nano)fragments called tumour-derived microvesicles (TMV) that are believed to play an important role in cancer progression. TMV suppress/modify antitumour response of the host, but there is also some evidence for their direct interaction with cancer ce...

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Autores principales: Stec, Małgorzata, Szatanek, Rafał, Baj-Krzyworzeka, Monika, Baran, Jarosław, Zembala, Maria, Barbasz, Jakub, Waligórska, Agnieszka, Dobrucki, Jurek W., Mytar, Bożenna, Szczepanik, Antoni, Siedlar, Maciej, Drabik, Grażyna, Urbanowicz, Barbara, Zembala, Marek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666152/
https://www.ncbi.nlm.nih.gov/pubmed/26626416
http://dx.doi.org/10.1186/s12967-015-0737-0
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author Stec, Małgorzata
Szatanek, Rafał
Baj-Krzyworzeka, Monika
Baran, Jarosław
Zembala, Maria
Barbasz, Jakub
Waligórska, Agnieszka
Dobrucki, Jurek W.
Mytar, Bożenna
Szczepanik, Antoni
Siedlar, Maciej
Drabik, Grażyna
Urbanowicz, Barbara
Zembala, Marek
author_facet Stec, Małgorzata
Szatanek, Rafał
Baj-Krzyworzeka, Monika
Baran, Jarosław
Zembala, Maria
Barbasz, Jakub
Waligórska, Agnieszka
Dobrucki, Jurek W.
Mytar, Bożenna
Szczepanik, Antoni
Siedlar, Maciej
Drabik, Grażyna
Urbanowicz, Barbara
Zembala, Marek
author_sort Stec, Małgorzata
collection PubMed
description BACKGROUND: Tumour cells release membrane micro(nano)fragments called tumour-derived microvesicles (TMV) that are believed to play an important role in cancer progression. TMV suppress/modify antitumour response of the host, but there is also some evidence for their direct interaction with cancer cells. In cancer patients TMV are present in body fluid and tumour microenvironment. The present study aimed at characterization of whole types/subpopulations, but not only exosomes, of TMV from newly established gastric cancer cell line (called GC1415) and to define their interactions with autologous cells. METHODS: TMV were isolated from cell cultures supernatants by centrifugation at 50,000×g and their phenotype was determined by flow cytometry. The size of TMV was analysed by dynamic light scattering and nanoparticle tracking analysis, while morphology by transmission electron microscopy and atomic force microscopy. Interactions of TMV with cancer cells were visualized using fluorescence-activated cell sorter, confocal and atomic force microscopy, biological effects by xenografts in NOD SCID mice. RESULTS: Isolated TMV showed expression of CD44H, CD44v6 (hyaluronian receptors), CCR6 (chemokine receptor) and HER-2/neu molecules, exhibited different shapes and sizes (range 60–900 nm, highest frequency of particles with size range of 80–120 nm). TMV attached to autologous cancer cells within 2 h and then were internalized by them at 24 h. CD44H, CD44v6 and CCR6 molecules may play a role in attachment of TMV to cancer cells, while HER-2 associated with CD24 be involved in promoting cancer cells growth. Pre-exposure of cancer cells to TMV resulted in enhancement of tumour growth and cancer cell-induced angiogenesis in NOD SCID mice model. CONCLUSIONS: TMV interact directly with cancer cells serving as macro-messengers and molecular cargo transfer between gastric cancer cells resulting in enhancement of tumour growth. TMV should be considered in future as target of anticancer therapy.
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spelling pubmed-46661522015-12-02 Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells Stec, Małgorzata Szatanek, Rafał Baj-Krzyworzeka, Monika Baran, Jarosław Zembala, Maria Barbasz, Jakub Waligórska, Agnieszka Dobrucki, Jurek W. Mytar, Bożenna Szczepanik, Antoni Siedlar, Maciej Drabik, Grażyna Urbanowicz, Barbara Zembala, Marek J Transl Med Research BACKGROUND: Tumour cells release membrane micro(nano)fragments called tumour-derived microvesicles (TMV) that are believed to play an important role in cancer progression. TMV suppress/modify antitumour response of the host, but there is also some evidence for their direct interaction with cancer cells. In cancer patients TMV are present in body fluid and tumour microenvironment. The present study aimed at characterization of whole types/subpopulations, but not only exosomes, of TMV from newly established gastric cancer cell line (called GC1415) and to define their interactions with autologous cells. METHODS: TMV were isolated from cell cultures supernatants by centrifugation at 50,000×g and their phenotype was determined by flow cytometry. The size of TMV was analysed by dynamic light scattering and nanoparticle tracking analysis, while morphology by transmission electron microscopy and atomic force microscopy. Interactions of TMV with cancer cells were visualized using fluorescence-activated cell sorter, confocal and atomic force microscopy, biological effects by xenografts in NOD SCID mice. RESULTS: Isolated TMV showed expression of CD44H, CD44v6 (hyaluronian receptors), CCR6 (chemokine receptor) and HER-2/neu molecules, exhibited different shapes and sizes (range 60–900 nm, highest frequency of particles with size range of 80–120 nm). TMV attached to autologous cancer cells within 2 h and then were internalized by them at 24 h. CD44H, CD44v6 and CCR6 molecules may play a role in attachment of TMV to cancer cells, while HER-2 associated with CD24 be involved in promoting cancer cells growth. Pre-exposure of cancer cells to TMV resulted in enhancement of tumour growth and cancer cell-induced angiogenesis in NOD SCID mice model. CONCLUSIONS: TMV interact directly with cancer cells serving as macro-messengers and molecular cargo transfer between gastric cancer cells resulting in enhancement of tumour growth. TMV should be considered in future as target of anticancer therapy. BioMed Central 2015-12-01 /pmc/articles/PMC4666152/ /pubmed/26626416 http://dx.doi.org/10.1186/s12967-015-0737-0 Text en © Stec et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Stec, Małgorzata
Szatanek, Rafał
Baj-Krzyworzeka, Monika
Baran, Jarosław
Zembala, Maria
Barbasz, Jakub
Waligórska, Agnieszka
Dobrucki, Jurek W.
Mytar, Bożenna
Szczepanik, Antoni
Siedlar, Maciej
Drabik, Grażyna
Urbanowicz, Barbara
Zembala, Marek
Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells
title Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells
title_full Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells
title_fullStr Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells
title_full_unstemmed Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells
title_short Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells
title_sort interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666152/
https://www.ncbi.nlm.nih.gov/pubmed/26626416
http://dx.doi.org/10.1186/s12967-015-0737-0
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