The Formation of Stable Lung Tumor Spheroids during Random Positioning Involves Increased Estrogen Sensitivity

Balkis Barkia; Viviann Sandt; Daniela Melnik; José Luis Cortés-Sánchez; Shannon Marchal; Bjorn Baselet; Sarah Baatout; Jayashree Sahana; Daniela Grimm; Markus Wehland; Herbert Schulz; Manfred Infanger; Armin Kraus; Marcus Krüger

doi:10.3390/biom14101292

The Formation of Stable Lung Tumor Spheroids during Random Positioning Involves Increased Estrogen Sensitivity

Balkis Barkia, Viviann Sandt, Daniela Melnik, José Luis Cortés-Sánchez, Shannon Marchal, Bjorn Baselet, Sarah Baatout, Jayashree Sahana, Daniela Grimm, Markus Wehland, Herbert Schulz, Manfred Infanger, Armin Kraus, Marcus Krüger

Institut for Biomedicin - Forskning og uddannelse, Vest

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

1 Citationer (Scopus)

Abstract

The formation of tumor spheroids on the random positioning machine (RPM) is a complex and important process, as it enables the study of metastasis ex vivo. However, this process is not yet understood in detail. In this study, we compared the RPM-induced spheroid formation of two cell types of lung carcinoma (NCI-H1703 squamous cell carcinoma cells and Calu-3 adenocarcinoma cells). While NCI-H1703 cells were mainly present as spheroids after 3 days of random positioning, Calu-3 cells remained predominantly as a cell layer. We found that two-dimensional-growing Calu-3 cells have less mucin-1, further downregulate their expression on the RPM and therefore exhibit a higher adhesiveness. In addition, we observed that Calu-3 cells can form spheroids, but they are unstable due to an imbalanced ratio of adhesion proteins (β1-integrin, E-cadherin) and anti-adhesion proteins (mucin-1) and are likely to disintegrate in the shear environment of the RPM. RPM-exposed Calu-3 cells showed a strongly upregulated expression of the estrogen receptor alpha gene ESR1. In the presence of 17β-estradiol or phenol red, more stable Calu-3 spheroids were formed, which was presumably related to an increased amount of E-cadherin in the cell aggregates. Thus, RPM-induced tumor spheroid formation depends not solely on cell-type-specific properties but also on the complex interplay between the mechanical influences of the RPM and, to some extent, the chemical composition of the medium used during the experiments.

Originalsprog	Engelsk
Artikelnummer	1292
Tidsskrift	Biomolecules
Vol/bind	14
Nummer	10
ISSN	2218-273X
DOI	https://doi.org/10.3390/biom14101292
Status	Udgivet - 12 okt. 2024

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10.3390/biom14101292Licens: CC BY

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Barkia, B., Sandt, V., Melnik, D., Cortés-Sánchez, J. L., Marchal, S., Baselet, B., Baatout, S., Sahana, J., Grimm, D., Wehland, M., Schulz, H., Infanger, M., Kraus, A., & Krüger, M. (2024). The Formation of Stable Lung Tumor Spheroids during Random Positioning Involves Increased Estrogen Sensitivity. Biomolecules, 14(10), Artikel 1292. https://doi.org/10.3390/biom14101292

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title = "The Formation of Stable Lung Tumor Spheroids during Random Positioning Involves Increased Estrogen Sensitivity",

abstract = "The formation of tumor spheroids on the random positioning machine (RPM) is a complex and important process, as it enables the study of metastasis ex vivo. However, this process is not yet understood in detail. In this study, we compared the RPM-induced spheroid formation of two cell types of lung carcinoma (NCI-H1703 squamous cell carcinoma cells and Calu-3 adenocarcinoma cells). While NCI-H1703 cells were mainly present as spheroids after 3 days of random positioning, Calu-3 cells remained predominantly as a cell layer. We found that two-dimensional-growing Calu-3 cells have less mucin-1, further downregulate their expression on the RPM and therefore exhibit a higher adhesiveness. In addition, we observed that Calu-3 cells can form spheroids, but they are unstable due to an imbalanced ratio of adhesion proteins (β1-integrin, E-cadherin) and anti-adhesion proteins (mucin-1) and are likely to disintegrate in the shear environment of the RPM. RPM-exposed Calu-3 cells showed a strongly upregulated expression of the estrogen receptor alpha gene ESR1. In the presence of 17β-estradiol or phenol red, more stable Calu-3 spheroids were formed, which was presumably related to an increased amount of E-cadherin in the cell aggregates. Thus, RPM-induced tumor spheroid formation depends not solely on cell-type-specific properties but also on the complex interplay between the mechanical influences of the RPM and, to some extent, the chemical composition of the medium used during the experiments.",

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author = "Balkis Barkia and Viviann Sandt and Daniela Melnik and Cort{\'e}s-S{\'a}nchez, {Jos{\'e} Luis} and Shannon Marchal and Bjorn Baselet and Sarah Baatout and Jayashree Sahana and Daniela Grimm and Markus Wehland and Herbert Schulz and Manfred Infanger and Armin Kraus and Marcus Kr{\"u}ger",

year = "2024",

month = oct,

day = "12",

doi = "10.3390/biom14101292",

language = "English",

volume = "14",

journal = "Biomolecules",

issn = "2218-273X",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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T1 - The Formation of Stable Lung Tumor Spheroids during Random Positioning Involves Increased Estrogen Sensitivity

AU - Barkia, Balkis

AU - Sandt, Viviann

AU - Melnik, Daniela

AU - Cortés-Sánchez, José Luis

AU - Marchal, Shannon

AU - Baselet, Bjorn

AU - Baatout, Sarah

AU - Sahana, Jayashree

AU - Grimm, Daniela

AU - Wehland, Markus

AU - Schulz, Herbert

AU - Infanger, Manfred

AU - Kraus, Armin

AU - Krüger, Marcus

PY - 2024/10/12

Y1 - 2024/10/12

N2 - The formation of tumor spheroids on the random positioning machine (RPM) is a complex and important process, as it enables the study of metastasis ex vivo. However, this process is not yet understood in detail. In this study, we compared the RPM-induced spheroid formation of two cell types of lung carcinoma (NCI-H1703 squamous cell carcinoma cells and Calu-3 adenocarcinoma cells). While NCI-H1703 cells were mainly present as spheroids after 3 days of random positioning, Calu-3 cells remained predominantly as a cell layer. We found that two-dimensional-growing Calu-3 cells have less mucin-1, further downregulate their expression on the RPM and therefore exhibit a higher adhesiveness. In addition, we observed that Calu-3 cells can form spheroids, but they are unstable due to an imbalanced ratio of adhesion proteins (β1-integrin, E-cadherin) and anti-adhesion proteins (mucin-1) and are likely to disintegrate in the shear environment of the RPM. RPM-exposed Calu-3 cells showed a strongly upregulated expression of the estrogen receptor alpha gene ESR1. In the presence of 17β-estradiol or phenol red, more stable Calu-3 spheroids were formed, which was presumably related to an increased amount of E-cadherin in the cell aggregates. Thus, RPM-induced tumor spheroid formation depends not solely on cell-type-specific properties but also on the complex interplay between the mechanical influences of the RPM and, to some extent, the chemical composition of the medium used during the experiments.

AB - The formation of tumor spheroids on the random positioning machine (RPM) is a complex and important process, as it enables the study of metastasis ex vivo. However, this process is not yet understood in detail. In this study, we compared the RPM-induced spheroid formation of two cell types of lung carcinoma (NCI-H1703 squamous cell carcinoma cells and Calu-3 adenocarcinoma cells). While NCI-H1703 cells were mainly present as spheroids after 3 days of random positioning, Calu-3 cells remained predominantly as a cell layer. We found that two-dimensional-growing Calu-3 cells have less mucin-1, further downregulate their expression on the RPM and therefore exhibit a higher adhesiveness. In addition, we observed that Calu-3 cells can form spheroids, but they are unstable due to an imbalanced ratio of adhesion proteins (β1-integrin, E-cadherin) and anti-adhesion proteins (mucin-1) and are likely to disintegrate in the shear environment of the RPM. RPM-exposed Calu-3 cells showed a strongly upregulated expression of the estrogen receptor alpha gene ESR1. In the presence of 17β-estradiol or phenol red, more stable Calu-3 spheroids were formed, which was presumably related to an increased amount of E-cadherin in the cell aggregates. Thus, RPM-induced tumor spheroid formation depends not solely on cell-type-specific properties but also on the complex interplay between the mechanical influences of the RPM and, to some extent, the chemical composition of the medium used during the experiments.

KW - Cadherins/metabolism

KW - Cell Adhesion/drug effects

KW - Cell Line, Tumor

KW - Estradiol/pharmacology

KW - Estrogen Receptor alpha/metabolism

KW - Estrogens/pharmacology

KW - Gene Expression Regulation, Neoplastic/drug effects

KW - Humans

KW - Integrin beta1/metabolism

KW - Lung Neoplasms/metabolism

KW - Mucin-1/metabolism

KW - Spheroids, Cellular/metabolism

KW - tumor spheroids

KW - lung cancer

KW - phenol red

KW - cell signaling

KW - simulated microgravity

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U2 - 10.3390/biom14101292

DO - 10.3390/biom14101292

M3 - Journal article

C2 - 39456226

SN - 2218-273X

VL - 14

JO - Biomolecules

JF - Biomolecules

IS - 10

M1 - 1292

ER -

The Formation of Stable Lung Tumor Spheroids during Random Positioning Involves Increased Estrogen Sensitivity

Abstract

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