Cell and extracellular matrix interaction models in benign mesothelial and malignant pleural mesothelioma cells in 2D and 3D in-vitro

Our plain-English summary of Cell and extracellular matrix interaction models in benign mesothelial and malignant pleural mesothelioma cells in 2D and 3D in-vitro, by R.M. Jagirdar, E.D. Papazoglou, E. Pitaraki, et al (Clinical and Experimental Pharmacology & Physiology, 2021).

The study

• Authors: R.M. Jagirdar, E.D. Papazoglou, E. Pitaraki, O.A. Kouliou, E. Rouka, L. Giannakou, S. Giannopoulos, S.I. Sinis, C. Hatzoglou, K.I. Gourgoulianis, S.G. Zarogiannis
• Journal: Clinical and Experimental Pharmacology & Physiology
• Published: 2021;48(4):543-552
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumour that grows in the pleural cavity. MPM spheroids released in the pleural fluid can form new tumour foci. Cell-cell, cell-extracellular matrix (ECM) interactions in 2D and 3D impact malignant cell behaviour during cell adhesion, migration, proliferation and epithelial-mesenchymal transition (EMT). In this study, epithelioid, biphasic and sarcomatoid MPM cell types as well as benign mesothelial cells were tested with regards to the above phenotypes. Fibronectin (FN) and homologous cell-derived extracellular matrix (hcd-ECM) treated substratum differentially affected the above phenotypes. 3D MPM spheroid invasion was higher in FN-collagen matrices in the epithelioid and biphasic cells, while 3D cell cultures of epithelioid and sarcomatoid MPM cells in FN-collagen showed a higher contractility compared to hcd-ECM-collagen. Cell aggregates demonstrated invasive behaviour in hcd-ECM matrices alone. Our results suggest that ECM and the dimensionality affect malignant cell behaviour during cell culture studies.

© 2020 John Wiley & Sons Australia, Ltd.

In plain English

This was a laboratory study of cultured cells. No people or animals were studied, and asbestos exposure was not tested. The authors compared four cell lines: MeT-5A (benign mesothelial cells, SV40 transformed), M14K (epithelioid malignant pleural mesothelioma), MSTO-211H (biphasic) and ZL34 (sarcomatoid). In flat (2D) cultures, each line grew on surfaces treated with plasma fibronectin (FN) or with matrix made by the same cell type (hcd-ECM). In three-dimensional (3D) cultures, FN or hcd-ECM was added to the medium or to collagen. All three mesothelioma lines stuck to hcd-ECM more than to FN; the benign cells showed no significant difference. In 2D cultures, all four lines migrated and multiplied more on FN. Mesothelioma spheroids (small balls of cells) grew larger with hcd-ECM. Spheroid invasion into collagen was higher with FN for the epithelioid and biphasic lines, but higher with hcd-ECM for the sarcomatoid line. Benign spheroids formed no invasive protrusions. In collagen gels, FN led to more contraction for the epithelioid and sarcomatoid lines. The authors concluded that the extracellular matrix and the dimensionality affect malignant cell behaviour during cell culture studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in-vitro) cell culture experiment comparing two extracellular matrix treatments in 2D and 3D assays
• Who was studied: Four human cell lines (no patients): MeT-5A benign mesothelial cells (SV40 transformed), M14K epithelioid MPM, MSTO-211H biphasic MPM, and ZL34 sarcomatoid MPM; work done at the University of Thessaly, Larissa, Greece
• Exposure: Not asbestos. In 2D assays, cells were grown on surfaces treated with plasma fibronectin (FN) or with homologous cell-derived extracellular matrix (hcd-ECM). In 3D assays, FN or hcd-ECM (250 ng/mL) was added to the culture medium or to collagen matrices.
• Main results:
  • Cell adhesion was significantly higher on hcd-ECM than on FN in all three MPM lines. For ZL34 (sarcomatoid), adhesion was 141.7 plus or minus 4.2% on hcd-ECM, with FN set at 100% (p less than .005). MeT-5A benign cells showed no significant difference.
  • In all four cell lines, 2D migration after wound healing was significantly higher on FN than on hcd-ECM.
  • 2D proliferation was significantly higher on FN in all cell lines. For example, in M14K cells the 72-hour fold change was 5.2 on FN versus 2.4 on hcd-ECM (p less than .005).
  • 3D spheroids of the MPM lines had a larger perimeter with hcd-ECM than with FN. For example, MSTO spheroids measured 132.4% with hcd-ECM versus 100.6% with FN (p less than .005). MeT-5A spheroids showed no significant size difference.
  • Spheroid invasion into collagen was higher with FN for the epithelioid line (M14K: 68.1% with hcd-ECM versus 100% with FN) and the biphasic line (MSTO: 70.1% versus 100%).
  • For the sarcomatoid line ZL34, spheroid invasion was higher with hcd-ECM: 159.8% versus 100.0% with FN (p less than .005).
  • Benign MeT-5A spheroids did not develop invasive protrusions with either FN or hcd-ECM.
  • In collagen gel contraction, gels with FN were smaller (meaning more contraction) than gels with hcd-ECM for M14K (100% versus 126.4%, p less than .005) and for ZL34 (99.4% versus 106.7%, p less than .01).
  • In the gel contraction assay, MeT-5A and MSTO cells showed no difference between FN and hcd-ECM.
  • In the cell aggregate assay, MPM aggregates showed invasive projections into collagen only with hcd-ECM. With FN, MPM aggregates took a compact, spindle-like shape. Benign cells showed minor invasive structures with both treatments.
• The authors' conclusion: The authors concluded that the extracellular matrix, and whether cells are grown in 2D or 3D, affect malignant cell behaviour in cell culture studies.
• Limitations the authors state:
  • The authors stated that their idea that invasion and contraction depend on particular integrins is a hypothesis requiring further investigation.
  • The authors stated that aggregate invasion still needs to be characterized.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pleural Cavity, Epithelioid, Biphasic Mesothelioma, Sarcomatoid, Mesothelial Cells, Collagen.

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