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Mechanical signals inhibit growth of a grafted tumor in vivo: Proof of Concept

Rémy Brossel, Alexandre Yahi, Stéphane David, Laura Moreno Velasquez, Jean-Marc Guinebretière
doi: https://doi.org/10.1101/045534
Rémy Brossel
1Cell Constraint & Cancer Inc (CC&C), Le mas l’Hermite, 331 chemin de la Poterie, 13280 Raphèle-les-Arles, France;
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Alexandre Yahi
2Institut Curie, 35 rue Dailly, 92210 Saint-Cloud, France. School of Electrical and Computer Engineering, College of Engineering, Georgia Institute of Technology, 777 Atlantic Dr NW, Atlanta, GA 30332-0250, USA; Supelec, 3 rue Joliot-Curie, Gif sur Yvette 91192 France;
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Stéphane David
3Altran Research, 2 rue Paul Dautier, 78140 Vèlizy-Villacoublay, France;
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Laura Moreno Velasquez
4Institut Curie, 35 rue Dailly, 92210 Saint-Cloud, France. Physiologie Intégrée du Système d’éveil, Centre de Recherches en Neurosciences de Lyon (CNRL), Inserm U1028, CNRS UMR5292, Faculté de médecine, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France;
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Jean-Marc Guinebretière
5Pathology Department, Hôpital René-Huguenin Institut Curie, 35 rue Dailly, 92210 Saint-Cloud, France.
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ABSTRACT

In the past ten years, many studies have shown that malignant tissue has been “normalized” in vitro using mechanical signals. We apply the principles of physical oncology (or mechanobiology) in vivo to show the effect of a “constraint field” on tumor growth. The human breast cancer cell line, MDA MB 231, admixed with ferric nanoparticles was grafted subcutaneously in Nude mice. The magnetizable particles rapidly surrounded the growing tumor. Two permanent magnets located on either side of the tumor created a gradient of magnetic field. Magnetic energy is transformed into mechanical energy by the particles acting as “bioactuators”, applying a constraint field and, by consequence, biomechanical stress to the tumor. This biomechanical treatment was applied 2 hours/day during 21 days, from Day 18 to Day 39 following tumor implantation. The study lasted 74 days. Palpable tumor was measured two times a week. There was a significant in vivo difference between the median volume of treated tumors and untreated controls in the mice measured up to D 74 (D 59 + population): (529 [346; 966] mm3 vs 1334 [256; 2106] mm3; p=0.015), treated mice having smaller tumors. The difference was not statistically significant in the group of mice measured at least to D 59 (D 59 population). On ex vivo examination, the surface of the tumor mass, measured on histologic sections, was less in the treated group, G1, than in the control groups: G2 (nanoparticles, no magnetic field), G3 (magnetic field, no nanoparticles), G4 (no nanoparticles, no magnetic field) in the D 59 population (Median left surface was significantly lower in G1 (5.6 [3.0; 42.4] mm2, p=0.005) than in G2 (20.8 [4.9; 34.3]), G3 (16.5 [13.2; 23.2]) and G4 (14.8 [1.8; 55.5]); Median right surface was significantly lower in G1 (4.7 [1.9; 29.2] mm2, p=0.015) than in G2 (25.0 [5.2; 55.0]), G3 (18.0 [14.6; 35.2]) and G4 (12.5 [1.5; 51.8]). There was no statistically significant difference in the day 59+ population. This is the first demonstration of the effect of stress on tumor growth in vivo suggesting that biomechanical intervention may have a high translational potential as a therapy in locally advanced tumors like pancreatic cancer or primary hepatic carcinoma for which no effective therapy is currently available.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 29, 2016.
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Mechanical signals inhibit growth of a grafted tumor in vivo: Proof of Concept
Rémy Brossel, Alexandre Yahi, Stéphane David, Laura Moreno Velasquez, Jean-Marc Guinebretière
bioRxiv 045534; doi: https://doi.org/10.1101/045534
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Mechanical signals inhibit growth of a grafted tumor in vivo: Proof of Concept
Rémy Brossel, Alexandre Yahi, Stéphane David, Laura Moreno Velasquez, Jean-Marc Guinebretière
bioRxiv 045534; doi: https://doi.org/10.1101/045534

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