Mechanical control of cell proliferation increases resistance to chemotherapeutic agents

Ilaria Francesca Rizzuti, Pietro Mascheroni, Silvia Arcucci, Zacchari Ben-Mériem, Audrey Prunet, Catherine Barentin, Charlotte Rivière, Hélène Delanoë-Ayari, Haralampos Hatzikirou, Julie Guillermet-Guibert, Morgan Delarue

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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.

Original languageBritish English
Article number128103
JournalPhysical Review Letters
Volume125
Issue number12
DOIs
StatePublished - Sep 2020

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