Magnetic Compression of Tumor Spheroids Increases Cell Proliferation In Vitro and Cancer Progression In Vivo

Abstract

A growing tumor is submitted to ever-evolving mechanical stress. Endoscopic procedures add additional constraints. However, the impact of mechanical forces on cancer progression is still debated. Herein, a set of magnetic methods is proposed to form tumor spheroids and to subject them to remote deformation, mimicking stent-imposed compression. Upon application of a permanent magnet, the magnetic tumor spheroids (formed from colon cancer cells or from glioblastoma cells) are compressed by 50% of their initial diameters. Such significant deformation triggers an increase in the spheroid proliferation for both cell lines, correlated with an increase in the number of proliferating cells toward its center and associated with an overexpression of the matrix metalloproteinase−9 (MMP−9). In vivo peritoneal injection of the spheroids made from colon cancer cells confirmed the increased aggressiveness of the compressed spheroids, with almost a doubling of the peritoneal cancer index (PCI), as compared with non-stimulated spheroids. Moreover, liver metastasis of labeled cells was observed only in animals grafted with stimulated spheroids. Altogether, these results demonstrate that a large compression of tumor spheroids enhances cancer proliferation and metastatic process and could have implications in clinical procedures where tumor compression plays a role.

Superparamagnetic Iron Oxide Nanoparticles for Targeted Cell Seeding: Magnetic Patterning and Magnetic 3D Cell Culture

“…Indeed, the mechanic stress during magnetic remote deformation triggered cancer cell proliferation. [ 87 ]…”

Surface tension of model tissues during malignant transformation and epithelial–mesenchymal transition

“…Most techniques used to mechanically stimulate spheroids involve confining them either by encapsulation ( Alessandri et al, 2013 ), application of osmotic pressure ( Montel et al, 2011 ), or compression between rigid plates. Magnetic compression, by contrast, utilizes magnetic nanoparticles ( Mazuel et al, 2015 ) to exert volume forces on the cells, mimicking the stress experienced by tumors due to extracellular matrix stiffening and abnormal tissue growth ( Mary et al, 2022 ).…”

Transducing compressive forces into cellular outputs in cancer and beyond

“…This adaptive behavior in response to compression is only unleashed when tumor cells are relieved from their confinement. Indeed, compression without confinement increases the proliferation of colon and glioblastoma cancer cells ( Mary et al, 2022 ).…”