Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Chick Embryo Experimental Platform for 3D Tissue Engineering Modelling of Cancer Micrometastases for Tumor Biology, Drug Development and Nanomaterials Testing

Anna Guller
* ,
Inga Kuschnerus
ORCID logo ,
Vlada Rozova
,
Annemarie Nadort
,
Yin Yao
,
Zahra Khabir
,
Alfonso Garcia-Bennett
ORCID logo ,
Liuen (Olivia) Liang
,
Aleksandra Polikarpova
,
Yi Qian
,
Ewa M. Goldys
* ,
Andrei Zvyagin
* ORCID logo
Version 1 : Received: 5 September 2021 / Approved: 6 September 2021 / Online: 6 September 2021 (11:46:54 CEST)

A peer-reviewed article of this Preprint also exists.

Guller, A.; Kuschnerus, I.; Rozova, V.; Nadort, A.; Yao, Y.; Khabir, Z.; Garcia-Bennett, A.; Liang, L.O.; Polikarpova, A.; Qian, Y.; Goldys, E.M.; Zvyagin, A.V. Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications. Biomedicines 2021, 9, 1578. Guller, A.; Kuschnerus, I.; Rozova, V.; Nadort, A.; Yao, Y.; Khabir, Z.; Garcia-Bennett, A.; Liang, L.O.; Polikarpova, A.; Qian, Y.; Goldys, E.M.; Zvyagin, A.V. Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications. Biomedicines 2021, 9, 1578.

Abstract

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. Here, 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 is built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellular-ized 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 com-partments 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 diag-nosis 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.

Keywords

chick embryo; 3D culture; tumor models in vitro; tissue engineering; metastasis; triple-negative breast cancer; liver; mesoporous silica nanoparticles; doxorubicin; micrometastasis

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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