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Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Herein, we introduce an in vitro/in vivo model of organ-spec...

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Autores principales: Guller, Anna, Kuschnerus, Inga, Rozova, Vlada, Nadort, Annemarie, Yao, Yin, Khabir, Zahra, Garcia-Bennett, Alfonso, Liang, Liuen (Olivia), Polikarpova, Aleksandra, Qian, Yi, Goldys, Ewa M., Zvyagin, Andrei V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615510/
https://www.ncbi.nlm.nih.gov/pubmed/34829808
http://dx.doi.org/10.3390/biomedicines9111578
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author Guller, Anna
Kuschnerus, Inga
Rozova, Vlada
Nadort, Annemarie
Yao, Yin
Khabir, Zahra
Garcia-Bennett, Alfonso
Liang, Liuen (Olivia)
Polikarpova, Aleksandra
Qian, Yi
Goldys, Ewa M.
Zvyagin, Andrei V.
author_facet Guller, Anna
Kuschnerus, Inga
Rozova, Vlada
Nadort, Annemarie
Yao, Yin
Khabir, Zahra
Garcia-Bennett, Alfonso
Liang, Liuen (Olivia)
Polikarpova, Aleksandra
Qian, Yi
Goldys, Ewa M.
Zvyagin, Andrei V.
author_sort Guller, Anna
collection PubMed
description Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Herein, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model was built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellularized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2–3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development, and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal compartments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diagnosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.
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spelling pubmed-86155102021-11-26 Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications Guller, Anna Kuschnerus, Inga Rozova, Vlada Nadort, Annemarie Yao, Yin Khabir, Zahra Garcia-Bennett, Alfonso Liang, Liuen (Olivia) Polikarpova, Aleksandra Qian, Yi Goldys, Ewa M. Zvyagin, Andrei V. Biomedicines Article Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Herein, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model was built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellularized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2–3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development, and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal compartments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diagnosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors. MDPI 2021-10-29 /pmc/articles/PMC8615510/ /pubmed/34829808 http://dx.doi.org/10.3390/biomedicines9111578 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guller, Anna
Kuschnerus, Inga
Rozova, Vlada
Nadort, Annemarie
Yao, Yin
Khabir, Zahra
Garcia-Bennett, Alfonso
Liang, Liuen (Olivia)
Polikarpova, Aleksandra
Qian, Yi
Goldys, Ewa M.
Zvyagin, Andrei V.
Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications
title Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications
title_full Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications
title_fullStr Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications
title_full_unstemmed Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications
title_short Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications
title_sort chick embryo experimental platform for micrometastases research in a 3d tissue engineering model: cancer biology, drug development, and nanotechnology applications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615510/
https://www.ncbi.nlm.nih.gov/pubmed/34829808
http://dx.doi.org/10.3390/biomedicines9111578
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