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Mechanical Control of Cell Proliferation Increases Resistance to Chemotherapeutic Agents.
Rizzuti, Ilaria Francesca Mascheroni, Pietro Arcucci, Silvia Ben-Mériem, Zacchari Prunet, Audrey Barentin, Catherine Rivière, Charlotte Delanoë-Ayari, Hélène Hatzikirou, Haralampos Guillermet-Guibert, Julie
Rizzuti, Ilaria Francesca
Mascheroni, Pietro
Arcucci, Silvia
Ben-Mériem, Zacchari
Prunet, Audrey
Barentin, Catherine
Rivière, Charlotte
Delanoë-Ayari, Hélène
Hatzikirou, Haralampos
Guillermet-Guibert, Julie
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2020-09-18
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Abstract
While many cellular mechanisms leading to chemotherapeutic resistance have been identified, there is an increasing realization that tumor-stroma interactions also play an important role. In particular, mechanical alterations are inherent to solid cancer progression and profoundly impact cell physiology. Here, we explore the influence of compressive stress on the efficacy of chemotherapeutics in pancreatic cancer spheroids. We find that increased compressive stress leads to decreased drug efficacy. Theoretical modeling and experiments suggest that mechanical stress decreases cell proliferation which in turn reduces the efficacy of chemotherapeutics that target proliferating cells. Our work highlights a mechanical form of drug resistance and suggests new strategies for therapy.
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Phys Rev Lett. 2020 Sep 18;125(12):128103. doi: 10.1103/PhysRevLett.125.128103.
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en
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1079-7114
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Attribution-NonCommercial-ShareAlike 4.0 International