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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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.

Original languageEnglish
Article number1292
JournalBiomolecules
Volume14
Issue10
ISSN2218-273X
DOIs
Publication statusPublished - 12 Oct 2024

Keywords

  • Cadherins/metabolism
  • Cell Adhesion/drug effects
  • Cell Line, Tumor
  • Estradiol/pharmacology
  • Estrogen Receptor alpha/metabolism
  • Estrogens/pharmacology
  • Gene Expression Regulation, Neoplastic/drug effects
  • Humans
  • Integrin beta1/metabolism
  • Lung Neoplasms/metabolism
  • Mucin-1/metabolism
  • Spheroids, Cellular/metabolism
  • tumor spheroids
  • lung cancer
  • phenol red
  • cell signaling
  • simulated microgravity

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