Tensile Forces Originating from Cancer Spheroids Facilitate Tumor Invasion.
The mechanical properties of tumors and the tumor environment provide important information for the progression and characterization of cancer. Tumors are surrounded by an extracellular matrix (ECM) dominated by collagen I. The geometrical and mechanical properties of the ECM play an important role for the initial step in the formation of metastasis, presented by the migration of malignant cells towards new settlements as well as the vascular and lymphatic system. The extent of this cell invasion into the ECM is a key medical marker for cancer prognosis. In vivo studies reveal an increased stiffness and different architecture of tumor tissue when compared to its healthy counterparts. The observed parallel collagen organization on the tumor border and radial arrangement at the invasion zone has raised the question about the mechanisms organizing these structures. Here we study the effect of contractile forces originated from model tumor spheroids embedded in a biomimetic collagen I matrix. We show that contractile forces act immediately after seeding and deform the ECM, thus leading to tensile radial forces within the matrix. Relaxation of this tension via cutting the collagen does reduce invasion, showing a mechanical relation between the tensile state of the ECM and invasion. In turn, these results suggest that tensile forces in the ECM facilitate invasion. Furthermore, simultaneous contraction of the ECM and tumor growth leads to the condensation and reorientation of the collagen at the spheroid's surface. We propose a tension-based model to explain the collagen organization and the onset of invasion by forces originating from the tumor.
Institut Curie, PSL Research University, CNRS, UMR 168, F-75005, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 168, F-75005, Paris, France.|Centre National de la Recherche Scientifique, UMR168, 25 rue d'Ulm, 75248 Paris cedex 05, France.|Zurich University of Applied Sciences, Institute of Chemistry and Biotechnology, Einsiedlerstrasse 31, 8820 Wädenswil, Switzerland.
Katarzyna S
KS
Kopanska
Institut Curie, PSL Research University, CNRS, UMR 168, F-75005, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 168, F-75005, Paris, France.|Centre National de la Recherche Scientifique, UMR168, 25 rue d'Ulm, 75248 Paris cedex 05, France.
Yara
Y
Alcheikh
Institute Curie, PSL Research University, CNRS, UMR 144, F-75005, Paris, France.
Ralitza
R
Staneva
Institute Curie, PSL Research University, CNRS, UMR 144, F-75005, Paris, France.
Danijela
D
Vignjevic
Institut Curie, PSL Research University, CNRS, UMR 168, F-75005, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 168, F-75005, Paris, France.|Centre National de la Recherche Scientifique, UMR168, 25 rue d'Ulm, 75248 Paris cedex 05, France.|Institute for Cell Biology, Center for Molecular Biology of Inflammation, Münster University, Münster, Germany.
Timo
T
Betz
D000818:Animals; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D018874:Spheroids, Cellular / Q000378:metabolism* / Q000473:pathology; D013718:Tensile Strength
D024042:Collagen Type I