Biophysical interactions between components of the tumor microenvironment promote metastasis

Dimitra Vasilaki; Athina Bakopoulou; Alexandros Tsouknidas; Elaine Johnstone; Konstantinos Michalakis

doi:10.1007/s12551-021-00811-y

Biophysical interactions between components of the tumor microenvironment promote metastasis

Biophys Rev. 2021 Jun 4;13(3):339-357. doi: 10.1007/s12551-021-00811-y. eCollection 2021 Jun.

Authors

Dimitra Vasilaki¹, Athina Bakopoulou¹, Alexandros Tsouknidas², Elaine Johnstone³, Konstantinos Michalakis^{1

4

5}

Affiliations

¹ Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
² Laboratory for Biomaterials and Computational Mechanics, Department of Mechanical Engineering, University of Western Macedonia, Kozani, Greece.
³ Department of Oncology, University of Oxford, Oxford, UK.
⁴ Division of Graduate Prosthodontics, Tufts University School of Dental Medicine, Boston, MA USA.
⁵ University of Oxford, Oxford, UK.

Abstract

During metastasis, tumor cells need to adapt to their dynamic microenvironment and modify their mechanical properties in response to both chemical and mechanical stimulation. Physical interactions occur between cancer cells and the surrounding matrix including cell movements and cell shape alterations through the process of mechanotransduction. The latter describes the translation of external mechanical cues into intracellular biochemical signaling. Reorganization of both the cytoskeleton and the extracellular matrix (ECM) plays a critical role in these spreading steps. Migrating tumor cells show increased motility in order to cross the tumor microenvironment, migrate through ECM and reach the bloodstream to the metastatic site. There are specific factors affecting these processes, as well as the survival of circulating tumor cells (CTC) in the blood flow until they finally invade the secondary tissue to form metastasis. This review aims to study the mechanisms of metastasis from a biomechanical perspective and investigate cell migration, with a focus on the alterations in the cytoskeleton through this journey and the effect of biologic fluids on metastasis. Understanding of the biophysical mechanisms that promote tumor metastasis may contribute successful therapeutic approaches in the fight against cancer.

Keywords: Actomyosin contractility; Cell mechanics; Circulating tumor cells; Cytoskeleton; Metastasis; Shear stress.

Publication types

Review