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Cancer cell migration depends on adjacent ASC and adipose spheroids in a 3D bioprinted breast cancer model

by Hannes Horder, David Böhringer, Nadine Endrizzi, Laura S Hildebrand, Alessandro Cianciosi, Sabrina Stecher, Franziska Dusi, Sophie Schweinitzer, Martin Watzling, Jürgen Groll, Tomasz Jüngst, Jörg Teßmar, Petra Bauer-Kreisel, Ben Fabry, Torsten Blunk
Abstract:
Abstract Breast cancer develops in close proximity to mammary adipose tissue and interactions with the local adipose environment have been shown to drive tumor progression. The specific role, however, of this complex tumor microenvironment in cancer cell migration still needs to be elucidated. Therefore, in this study, a 3D bioprinted breast cancer model was developed that allows for a comprehensive analysis of individual tumor cell migration parameters in dependence of adjacent adipose stroma. In this co-culture model, a breast cancer compartment with MDA-MB-231 breast cancer cells embedded in collagen is surrounded by an adipose tissue compartment consisting of adipose-derived stromal cell (ASC) or adipose spheroids in a printable bioink based on thiolated hyaluronic acid. Printing parameters were optimized for adipose spheroids to ensure viability and integrity of the fragile lipid-laden cells. Preservation of the adipogenic phenotype after printing was demonstrated by quantification of lipid content, expression of adipogenic marker genes, the presence of a coherent adipo-specific extracellular matrix, and cytokine secretion. The migration of tumor cells as a function of paracrine signaling of the surrounding adipose compartment was then analyzed using live-cell imaging. The presence of ASC or adipose spheroids substantially increased key migration parameters of MDA-MB-231 cells, namely motile fraction, persistence, invasion distance, and speed. These findings shed new light on the role of adipose tissue in cancer cell migration. They highlight the potential of our 3D printed breast cancer-stroma model to elucidate mechanisms of stroma-induced cancer cell migration and to serve as a screening platform for novel anti-cancer drugs targeting cancer cell dissemination.
Reference:
Hannes Horder, David Böhringer, Nadine Endrizzi, Laura S Hildebrand, Alessandro Cianciosi, Sabrina Stecher, Franziska Dusi, Sophie Schweinitzer, Martin Watzling, Jürgen Groll, Tomasz Jüngst, Jörg Teßmar, Petra Bauer-Kreisel, Ben Fabry, Torsten BlunkCancer cell migration depends on adjacent ASC and adipose spheroids in a 3D bioprinted breast cancer modelIn Biofabrication, volume 16, 2024.
Bibtex Entry:
@article{horder_cancer_2024,
	title = {Cancer cell migration depends on adjacent {ASC} and adipose spheroids in a {3D} bioprinted breast cancer model},
	volume = {16},
	issn = {1758-5082, 1758-5090},
	url = {Horder Biofabrication 2024.pdf},
	doi = {10.1088/1758-5090/ad57f7},
	abstract = {Abstract
            Breast cancer develops in close proximity to mammary adipose tissue and interactions with the local adipose environment have been shown to drive tumor progression. The specific role, however, of this complex tumor microenvironment in cancer cell migration still needs to be elucidated. Therefore, in this study, a 3D bioprinted breast cancer model was developed that allows for a comprehensive analysis of individual tumor cell migration parameters in dependence of adjacent adipose stroma. In this co-culture model, a breast cancer compartment with MDA-MB-231 breast cancer cells embedded in collagen is surrounded by an adipose tissue compartment consisting of adipose-derived stromal cell (ASC) or adipose spheroids in a printable bioink based on thiolated hyaluronic acid. Printing parameters were optimized for adipose spheroids to ensure viability and integrity of the fragile lipid-laden cells. Preservation of the adipogenic phenotype after printing was demonstrated by quantification of lipid content, expression of adipogenic marker genes, the presence of a coherent adipo-specific extracellular matrix, and cytokine secretion. The migration of tumor cells as a function of paracrine signaling of the surrounding adipose compartment was then analyzed using live-cell imaging. The presence of ASC or adipose spheroids substantially increased key migration parameters of MDA-MB-231 cells, namely motile fraction, persistence, invasion distance, and speed. These findings shed new light on the role of adipose tissue in cancer cell migration. They highlight the potential of our 3D printed breast cancer-stroma model to elucidate mechanisms of stroma-induced cancer cell migration and to serve as a screening platform for novel anti-cancer drugs targeting cancer cell dissemination.},
	number = {3},
	urldate = {2024-09-10},
	journal = {Biofabrication},
	author = {Horder, Hannes and Böhringer, David and Endrizzi, Nadine and Hildebrand, Laura S and Cianciosi, Alessandro and Stecher, Sabrina and Dusi, Franziska and Schweinitzer, Sophie and Watzling, Martin and Groll, Jürgen and Jüngst, Tomasz and Teßmar, Jörg and Bauer-Kreisel, Petra and Fabry, Ben and Blunk, Torsten},
	month = jul,
	year = {2024},
	pages = {035031},
}