Original Article
Hyperthermia affects collagen fiber architecture and induces apoptosis in pancreatic and fibroblast tumor hetero-spheroids in vitro

https://doi.org/10.1016/j.nano.2020.102183Get rights and content
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Abstract

Desmoplasia, an aberrant production of extracellular matrix (ECM), is considered as one predictive marker of malignancy of pancreatic cancer. In this paper, we study the effect of mild hyperthermia on fibrillary collagen architecture in murine Achilles tendons and in a pancreatic cancer model, in vitro, i.e. 3D hetero-type tumor spheroids, consisting of pancreatic cancer (Panc-1) cells and fibroblasts (WI-38), producing collagen fibers. We clearly demonstrate that i) mild hyperthermia (40 °C, 42 °C) damages the collagen architecture in murine Achilles tendons. ii) Mild extrinsic (hot air) and iron oxide nanoparticle based magnetic hyperthermia reduce the level of collagen fiber architecture in the generated hetero-type tumor spheroids. iii) Mild magnetic hyperthermia reduces cell vitality mainly through apoptotic and necrotic processes in the generated tumor spheroids. In conclusion, hetero-type 3D tumor spheroids are suitable for studying the effect of hyperthermia on collagen fibers, in vitro.

Graphical Abstract

Mild hyperthermia affects the fibrillary collagen architecture of pancreatic hetero-type tumor spheroids and induces cell death via apoptosis and necrosis.

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Key words

Desmoplasia
Fibrillary collagen
Pancreatic cancer
Hetero-type tumor spheroids
Mild hyperthermia

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Disclosure: Ingrid Hilger declares that she is holding a patent DE 10 2005 062 746. Conflict of interest statement/financial support information: The authors report no conflict of interest in this work.

Acknowledgements

This work was funded by the European Commission (NoCanTher, EC685795), in part by the Federal Ministry of Education and Research (BMBF, grant number 03XP0003) and by the Interdisciplinary Center of Clinical Research (IZKF) of the University Hospital Jena. We thank Julia Göring and Susann Burgold for their excellent technical support and the Jena Biophotonics and Imaging Laboratory (JBIL) for providing the multiphoton microscope. We are thankful to Dr. Katja Grün (University Hospital Jena) for her support in performing histochemistry.

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These authors contributed equally.