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Multicellular spheroids as an in vitro tumor model

G Hamilton1

  • 1Ludwig Boltzmann Institute of Clinical Oncology, KH Lainz, Vienna, Austria. hamilton@netway.at

Cancer Letters
|December 5, 1998
PubMed
Summary

Multicellular spheroids (MCS) model tumor drug resistance by mimicking micrometastases. Understanding MCS limitations is crucial for improving in vitro cancer research and drug development.

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Cases.

Edinburgh medical and surgical journal·2018

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Multicellular spheroids (MCS) serve as in vitro models for tumor microenvironments, including micrometastases and avascular regions.
  • MCS are utilized to study drug resistance mechanisms, particularly those dependent on cell adhesion.
  • Known factors contributing to multicellular drug resistance include limited drug penetration, active drug efflux, cell quiescence, and adverse microenvironmental conditions (e.g., low pH, hypoxia).

Purpose of the Study:

  • To investigate the mechanisms of cell adhesion-dependent drug resistance in multicellular spheroids.
  • To explore the potential of chemosensitizers and adhesion-reversing agents in overcoming this resistance.
  • To identify and address the limitations of multicellular spheroids as accurate tumor models.

Main Methods:

  • Utilizing multicellular spheroids as a model system to simulate tumor micrometastases and avascular zones.
  • Investigating drug resistance in relation to cell adhesion properties.
  • Assessing the efficacy of chemosensitizers and adhesion-reversing agents in overcoming multicellular drug resistance.

Main Results:

  • Multicellular drug resistance is associated with factors like poor drug accessibility, active drug efflux, and cell quiescence in deeper spheroid layers.
  • Adverse microenvironmental conditions within spheroids, such as acidic pH and hypoxia, contribute to drug resistance.
  • The study highlights limitations in current MCS models, including incomplete understanding of core cell death mechanisms and the role of extracellular matrix (ECM) production.

Conclusions:

  • Multicellular spheroids offer a valuable, albeit imperfect, model for studying drug resistance in avascular tumor regions.
  • Further research is needed to elucidate core cell death pathways and the influence of ECM in MCS.
  • Addressing the limitations of MCS models is essential for advancing in vitro cancer drug development and chemosensitizer research.

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