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Mieulet V, Garnier C, Kieffer Y, et al. Stiffness increases with myofibroblast content and collagen density in mesenchymal high grade serous ovarian cancer. Sci Rep. 2021;11(1):4219doi: 10.1038/s41598-021-83685-0.
Mieulet, V., Garnier, C., Kieffer, Y., Guilbert, T., Nemati, F., Marangoni, E., Renault, G., Chamming's, F., Vincent-Salomon, A., & Mechta-Grigoriou, F. (2021). Stiffness increases with myofibroblast content and collagen density in mesenchymal high grade serous ovarian cancer. Scientific reports, 11(1), 4219. https://doi.org/10.1038/s41598-021-83685-0
Mieulet, Virginie, et al. "Stiffness increases with myofibroblast content and collagen density in mesenchymal high grade serous ovarian cancer." Scientific reports vol. 11,1 (2021): 4219. doi: https://doi.org/10.1038/s41598-021-83685-0
Mieulet V, Garnier C, Kieffer Y, Guilbert T, Nemati F, Marangoni E, Renault G, Chamming's F, Vincent-Salomon A, Mechta-Grigoriou F. Stiffness increases with myofibroblast content and collagen density in mesenchymal high grade serous ovarian cancer. Sci Rep. 2021 Feb 18;11(1):4219. doi: 10.1038/s41598-021-83685-0. PMID: 33603134; PMCID: PMC7892556.
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Sci Rep. 2021 Feb 18;11(1):4219. doi: 10.1038/s41598-021-83685-0.

Stiffness increases with myofibroblast content and collagen density in mesenchymal high grade serous ovarian cancer.

Scientific reports

Virginie Mieulet, Camille Garnier, Yann Kieffer, Thomas Guilbert, Fariba Nemati, Elisabetta Marangoni, Gilles Renault, Foucauld Chamming's, Anne Vincent-Salomon, Fatima Mechta-Grigoriou

Affiliations

  1. Stress and Cancer Laboratory, Institut Curie, PSL Research University, Equipe labelisée Ligue Nationale Contre le Cancer, 26, rue d'Ulm, 75248, Paris Cedex 05, France. [email protected].
  2. Inserm, U830, 75248, Paris, France. [email protected].
  3. Stress and Cancer Laboratory, Institut Curie, PSL Research University, Equipe labelisée Ligue Nationale Contre le Cancer, 26, rue d'Ulm, 75248, Paris Cedex 05, France.
  4. Inserm, U830, 75248, Paris, France.
  5. IMAG'IC Facility, Institut Cochin, INSERM U1016, CNRS UMR 8104, Université de Paris UMR-S1016, 75014, Paris, France.
  6. Laboratory of Preclinical Investigation, Institut Curie, 26, rue d'Ulm, 75248, Paris Cedex 05, France.
  7. Life Imaging Facility, University of Paris, "Imageries du Vivant" (PIV) Platform, Institut Cochin, 22 rue Mechain, 75014, Paris, France.
  8. Assistance publique-hôpitaux de Paris, HU Paris Ouest Site Georges Pompidou, 20 rue Leblanc, 75015, Paris, France.
  9. Department of Diagnostic and Theranostic Medicine, Institut Curie Hospital Group, 26, rue d'Ulm, 75248, Paris Cedex 05, France.
  10. Stress and Cancer Laboratory, Institut Curie, PSL Research University, Equipe labelisée Ligue Nationale Contre le Cancer, 26, rue d'Ulm, 75248, Paris Cedex 05, France. [email protected].
  11. Inserm, U830, 75248, Paris, France. [email protected].

PMID: 33603134 PMCID: PMC7892556 DOI: 10.1038/s41598-021-83685-0

Abstract

Women diagnosed with high-grade serous ovarian cancers (HGSOC) are still likely to exhibit a bad prognosis, particularly when suffering from HGSOC of the Mesenchymal molecular subtype (50% cases). These tumors show a desmoplastic reaction with accumulation of extracellular matrix proteins and high content of cancer-associated fibroblasts. Using patient-derived xenograft mouse models of Mesenchymal and Non-Mesenchymal HGSOC, we show here that HGSOC exhibit distinct stiffness depending on their molecular subtype. Indeed, tumor stiffness strongly correlates with tumor growth in Mesenchymal HGSOC, while Non-Mesenchymal tumors remain soft. Moreover, we observe that tumor stiffening is associated with high stromal content, collagen network remodeling, and MAPK/MEK pathway activation. Furthermore, tumor stiffness accompanies a glycolytic metabolic switch in the epithelial compartment, as expected based on Warburg's effect, but also in stromal cells. This effect is restricted to the central part of stiff Mesenchymal tumors. Indeed, stiff Mesenchymal tumors remain softer at the periphery than at the core, with stromal cells secreting high levels of collagens and showing an OXPHOS metabolism. Thus, our study suggests that tumor stiffness could be at the crossroad of three major processes, i.e. matrix remodeling, MEK activation and stromal metabolic switch that might explain at least in part Mesenchymal HGSOC aggressiveness.

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