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The Physics Of Cancer: The Role Of Physical Interactions And Mechanical Forces In Metastasis
D. Wirtz, K. Konstantopoulos, P. Searson
Published 2011 · Biology, Physics, Medicine
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Metastasis is a complex, multistep process responsible for >90% of cancer-related deaths. In addition to genetic and external environmental factors, the physical interactions of cancer cells with their microenvironment, as well as their modulation by mechanical forces, are key determinants of the metastatic process. We reconstruct the metastatic process and describe the importance of key physical and mechanical processes at each step of the cascade. The emerging insight into these physical interactions may help to solve some long-standing questions in disease progression and may lead to new approaches to developing cancer diagnostics and therapies.
This paper references
ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix
Michele A. Wozniak (2003)
Platelet glycoprotein VI facilitates experimental lung metastasis in syngenic mouse models
S. Jain (2009)
Cell movement is guided by the rigidity of the substrate.
C. Lo (2000)
Metastasis: Dissemination and growth of cancer cells in metastatic sites
A. Chambers (2002)
Extracellular matrix stiffness and architecture govern intracellular rheology in cancer.
E. L. Baker (2009)
Environmental sensing through focal adhesions
B. Geiger (2009)
Patterns of Metastasis
L. Weiss (2004)
Cell shape and cell division.
M. Théry (2006)
Micropipette aspiration of living cells.
R. Hochmuth (2000)
Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited
F. Sabeh (2009)
The Genomic Landscapes of Human Breast and Colorectal Cancers
L. Wood (2007)
Mechanotransduction in the renal tubule.
S. Weinbaum (2010)
Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions
O. J. McCarty (2000)
Application of direct current electric fields to cells and tissues in vitro and modulation of wound electric field in vivo
B. Song (2007)
The expression of fascin, an actin-bundling motility protein, correlates with hormone receptor-negative breast cancer and a more aggressive clinical course.
B. Yoder (2005)
Spontaneous migration of cancer cells under conditions of mechanical confinement.
D. Irimia (2009)
Distinct kinetic and mechanical properties govern selectin-leukocyte interactions
William D. Hanley (2004)
Cytoskeletal Cross-linking and Bundling in Motor-Independent Contraction
S. Sun (2010)
Platelets and cancer.
G. Nash (2002)
Tensional homeostasis and the malignant phenotype.
Matthew J. Paszek (2005)
Matrix Elasticity Directs Stem Cell Lineage Specification
A. Engler (2006)
Programmed subcellular release for studying the dynamics of cell detachment
Bridget E Wildt (2009)
Simultaneous imaging of GFP, CFP and collagen in tumors in vivo using multiphoton microscopy
E. Sahai (2005)
Slow viscous motion of a sphere parallel to a plane wall
A. Goldman (1967)
Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis
E. Sahai (2003)
Force measurements by micromanipulation of a single actin filament by glass needles
A. Kishino (1988)
Physical plasticity of the nucleus in stem cell differentiation
J. D. Pajerowski (2007)
Circulating tumor cells: detection, molecular profiling and future prospects
K. Jacob (2007)
Dysfunctional connections between the nucleus and the actin and microtubule networks in laminopathic models.
C. M. Hale (2008)
The kinetics of two dimensional TCR and pMHC interactions determine T cell responsiveness
Jun Huang (2010)
L-selectin facilitation of metastasis involves temporal induction of Fut7-dependent ligands at sites of tumor cell arrest.
H. Läubli (2006)
A distinctive role for focal adhesion proteins in three-dimensional cell motility
S. Fraley (2010)
Intravital imaging of metastatic behavior through a mammary imaging window
D. Kedrin (2008)
Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion.
T. Yeung (2005)
Cellular Motility Driven by Assembly and Disassembly of Actin Filaments
T. Pollard (2003)
Shear stress induces internalization of E‐cadherin and invasiveness in metastatic oesophageal cancer cells by a Src‐dependent pathway
K. Lawler (2009)
Triggering cell detachment from patterned electrode arrays by programmed subcellular release
Bridget E Wildt (2010)
Neurite growth in 3D collagen gels with gradients of mechanical properties
H. Sundararaghavan (2009)
Ballistic intracellular nanorheology reveals ROCK-hard cytoplasmic stiffening response to fluid flow
J. H. Lee (2006)
Force-Induced Unfolding of Fibronectin in the Extracellular Matrix of Living Cells
M. Smith (2007)
Epithelial contact guidance on well-defined micro- and nanostructured substrates
A. I. Teixeira (2003)
Acknowledgements The authors gratefully acknowledge support from the US National Institutes of Health (grants U54CA143868, U54CA151838 and RO1CA101135)
Capturing complex 3D tissue physiology in vitro
L. Griffith (2006)
Cell Migration: A Physically Integrated Molecular Process
D. Lauffenburger (1996)
Fluorescence correlation spectroscopy. II. An experimental realization
D. Magde (1974)
Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence.
J. Guck (2005)
Tumor cell cycle arrest induced by shear stress: Roles of integrins and Smad
Shun-Fu Chang (2008)
Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flow.
M. Burdick (2004)
unc-83 encodes a novel component of the nuclear envelope and is essential for proper nuclear migration.
Daniel A Starr (2001)
Role of 3 Integrins in Melanoma Cell Adhesion to Activated Platelets under Flow (*)
B. Felding-Habermann (1996)
Tensile regulation of axonal elongation and initiation
J. Zheng (1991)
Illuminating single molecules in condensed matter.
W. E. Moerner (1999)
Micro-organization and visco-elasticity of the interphase nucleus revealed by particle nanotracking
Y. Tseng (2004)
A Light and Electron Microscopic Study
J. Vuletin (1976)
Mechanisms for Flow-Enhanced Cell Adhesion
C. Zhu (2008)
Contribution of platelets to tumour metastasis
Laurie J. Gay (2011)
Inhibition of colon carcinoma cell lung colony formation by a soluble form of E-selectin.
G. Mannori (1997)
Mechanical load induces a 100-fold increase in the rate of collagen proteolysis by MMP-1.
A. Adhikari (2011)
Antimetastatic effects associated with platelet reduction.
G. Gasic (1968)
From micro- to nanofabrication with soft materials.
S. Quake (2000)
Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness
S. Palecek (1997)
Hydrodynamic Shear Regulates the Kinetics and Receptor Specificity of Polymorphonuclear Leukocyte-Colon Carcinoma Cell Adhesive Interactions1
S. Jadhav (2001)
Efficient cell migration requires global chromatin condensation
Gabi Gerlitz (2010)
S. Gerecht (2006)
The basics of epithelial-mesenchymal transition.
R. Kalluri (2009)
Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis
L. Borsig (2002)
Biological length scale topography enhances cell-substratum adhesion of human corneal epithelial cells
Nancy W. Karuri (2004)
Activation of Endogenous Cdc42 Visualized in Living Cells
Perihan Nalbant (2004)
The Drosophila KASH domain proteins Msp-300 and Klarsicht and the SUN domain protein Klaroid have no essential function during oogenesis
Martin Technau (2008)
Molecular basis of metastasis.
A. Varki (2009)
Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells.
S. N. Thomas (2009)
Real-time imaging reveals the single steps of brain metastasis formation
Y. Kienast (2010)
Mapping local matrix remodeling induced by a migrating tumor cell using three-dimensional multiple-particle tracking.
Ryan J. Bloom (2008)
Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis.
M. Zaman (2006)
Cell Migration: Integrating Signals from Front to Back
A. Ridley (2003)
Electrotaxis of lung cancer cells in a multiple-electric-field chip.
Ching-Wen Huang (2009)
Microrheology and ROCK signaling of human endothelial cells embedded in a 3D matrix.
P. Panorchan (2006)
Cancer cells in transit: the vascular interactions of tumor cells.
K. Konstantopoulos (2009)
Imaging Intracellular Fluorescent Proteins at Nanometer Resolution
E. Betzig (2006)
A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses.
S. Weinbaum (1994)
Viscoelastic retraction of single living stress fibers and its impact on cell shape, cytoskeletal organization, and extracellular matrix mechanics.
S. Kumar (2006)
Cell structure and dynamics.
A. Ridley (2011)
Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration.
J. H. Lee (2007)
Interplay of RhoA and motility in the programmed spreading of daughter cells postmitosis.
P. Mali (2010)
The seed and soil hypothesis: vascularisation and brain metastases.
I. Fidler (2002)
A perinuclear actin cap regulates nuclear shape
Shyam B. Khatau (2009)
The Distribution of Active Force Generators Controls Mitotic Spindle Position
S. Grill (2003)
The effect of actin disrupting agents on contact guidance of human embryonic stem cells.
S. Gerecht (2007)
Asymmetric enrichment of PIE-1 in the Caenorhabditis elegans zygote mediated by binary counterdiffusion
Brian R. Daniels (2009)
Matrix density-induced mechanoregulation of breast cell phenotype, signaling, and gene expression through a FAK-ERK linkage
P. Provenzano (2009)
Quantification of cell adhesion using a spinning disc device and application to surface-reactive materials.
A. García (1997)
The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited
I. Fidler (2003)
Kinetic modelling approaches to in vivo imaging
R. Phair (2001)
Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow.
M. Burdick (2003)
Nuclear Movement Regulated by Cdc42, MRCK, Myosin, and Actin Flow Establishes MTOC Polarization in Migrating Cells
E. Gomes (2005)
Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo.
S. Karpatkin (1988)
Myosin IIA dependent retrograde flow drives 3D cell migration.
Wenting Shih (2010)
Matrix elasticity, cytoskeletal forces and physics of the nucleus: how deeply do cells ‘feel’ outside and in?
A. Buxboim (2010)
Activation of tumor cell integrin αvβ3 controls angiogenesis and metastatic growth in the brain
M. Lorger (2009)
The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber
K. Dahl (2004)
Magnetic microposts for mechanical stimulation of biological cells: fabrication, characterization, and analysis.
N. Sniadecki (2008)
Direct observation of catch bonds involving cell-adhesion molecules
B. Marshall (2003)
Mechanical loading of bovine pericardium accelerates enzymatic degradation.
J. Ellsmere (1999)
A Perspective on Cancer Cell Metastasis
Christine L Chaffer (2011)
Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis.
E. Camerer (2004)
α-Catenin mediates initial E-cadherin-dependent cell–cell recognition and subsequent bond strengthening
Saumendra Bajpai (2008)
Membrane Type I Matrix Metalloproteinase Usurps Tumor Growth Control Imposed by the Three-Dimensional Extracellular Matrix
K. Hotary (2003)
Cancer cell stiffness: integrated roles of three-dimensional matrix stiffness and transforming potential.
E. L. Baker (2010)
Intracellular microrheology of motile Amoeba proteus.
S. S. Rogers (2008)
Loss of α-Catenin Decreases the Strength of Single E-cadherin Bonds between Human Cancer Cells*
Saumendra Bajpai (2009)
Dynamic cell stretching increases human osteoblast proliferation and CICP synthesis but decreases osteocalcin synthesis and alkaline phosphatase activity.
D. Kaspar (2000)
Fibronectin fibrillogenesis regulates three-dimensional neovessel formation.
X. Zhou (2008)
Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness.
P. Stewart-Hutchinson (2008)
Coupling of the nucleus and cytoplasm
Melissa Crisp (2006)
A cancer cell metalloprotease triad regulates the basement membrane transmigration program.
K. Hotary (2006)
Particle-tracking microrheology of living cells: principles and applications.
D. Wirtz (2009)
Fluorescence correlation spectroscopy
W. Webb (2000)
Cadherin-mediated cell sorting not determined by binding or adhesion specificity
C. Niessen (2002)
Shear stress–induced endothelial cell polarization is mediated by Rho and Rac but not Cdc42 or PI 3-kinases
B. Wojciak-Stothard (2003)
Contact guidance mediated three-dimensional cell migration is regulated by Rho/ROCK-dependent matrix reorganization.
P. Provenzano (2008)
High mobility of proteins in the mammalian cell nucleus
R. Phair (2000)
Collective migration of an epithelial monolayer in response to a model wound
M. Poujade (2007)
The inner lives of focal adhesions.
B. Wehrle-Haller (2002)
Nascent Focal Adhesions Are Responsible for the Generation of Strong Propulsive Forces in Migrating Fibroblasts
K. Beningo (2001)
Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo
S. Grill (2001)
Intravital microscopy: new insights into metastasis of tumors
E. Beerling (2011)
Designing biosensors for Rho family proteins — deciphering the dynamics of Rho family GTPase activation in living cells
O. Pertz (2004)
Involvement of platelets in tumour angiogenesis?
H. Pinedo (1998)
Lysis of tumor cells by natural killer cells in mice is impeded by platelets.
B. Nieswandt (1999)
Carcinoembryonic Antigen and CD44 Variant Isoforms Cooperate to Mediate Colon Carcinoma Cell Adhesion to E- and L-selectin in Shear Flow*
S. N. Thomas (2008)
WASP and WAVE family proteins: Friends or foes in cancer invasion?
S. Kurisu (2010)
Three-Dimensional Super-Resolution Imaging by Stochastic Optical Reconstruction Microscopy
B. Huang (2008)
Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits
K. Polyak (2009)
Intravital imaging of cell movement in tumours
J. Condeelis (2003)
ANChors away: an actin based mechanism of nuclear positioning
Daniel A Starr (2003)
Cells lying on a bed of microneedles: An approach to isolate mechanical force
John L. Tan (2003)
Mechanics, malignancy, and metastasis: The force journey of a tumor cell
S. Kumar (2008)
Mechanotransduction across the cell surface and through the cytoskeleton
Ning Wang (1993)
Geometric control of cell life and death.
C. Chen (1997)
Nanomechanical analysis of cells from cancer patients.
S. E. Cross (2007)
The forward rate of binding of surface-tethered reactants: effect of relative motion between two surfaces.
K. Chang (1999)
Cdc42 mediates nucleus movement and MTOC polarization in Swiss 3T3 fibroblasts under mechanical shear stress.
J. H. Lee (2005)
Tumor metastasis: mechanistic insights and clinical challenges
P. Steeg (2006)
Single-molecule binding of CD44 to fibrin versus P-selectin predicts their distinct shear-dependent interactions in cancer
P. S. Raman (2011)
CD44 activation and associated primary adhesion is inducible via T cell receptor stimulation.
H. Degrendele (1997)
Comments on hematogenous metastatic patterns in humans as revealed by autopsy
L. Weiss (2004)
Complex networks orchestrate epithelial–mesenchymal transitions
J. Thiery (2006)
Stresses at the cell-to-substrate interface during locomotion of fibroblasts.
M. Dembo (1999)
Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants.
Duke Duguay (2003)
Micromechanical coupling between cell surface receptors and RGD peptides.
A. Rahman (2002)
Single-molecule analysis of cadherin-mediated cell-cell adhesion
P. Panorchan (2006)
Noninvasive assessment of collagen gel microstructure and mechanics using multiphoton microscopy.
C. Raub (2007)
Integrins: bidirectional, allosteric signaling
R. O. Hynes (2002)
Competing interests statement
One-dimensional topography underlies three-dimensional fibrillar cell migration
A. Doyle (2009)
Fibroblast adaptation and stiffness matching to soft elastic substrates.
Jérôme Solon (2007)
Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease
M. Mycielska (2004)
Nuclear mechanics during cell migration.
P. Friedl (2011)
Super-resolution fluorescence microscopy.
B. Huang (2009)
Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction.
J. Lammerding (2004)
Platelet glycoprotein Ibα supports experimental lung metastasis
S. Jain (2007)
Probing single-cell micromechanics in vivo: the microrheology of C. elegans developing embryos.
Brian R. Daniels (2006)
Microfluidics technology for systems biology research.
C. J. Wang (2009)
Stromal myofibroblasts are drivers of invasive cancer growth
O. De Wever (2008)
Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
K. R. Levental (2009)
Redirection of tumor metastasis by expression of E-selectin in vivo
L. Biancone (1996)
Simple and rapid process for single cell micro-patterning.
Ammar Azioune (2009)
Biomaterials in Tissue Engineering
J. Hubbell (1995)
Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6
C. Hidalgo-Carcedo (2011)
MT1‐MMP expression promotes tumor growth and angiogenesis through an up‐regulation of vascular endothelial growth factor expression
N. E. Sounni (2002)
Cell adhesion: integrating cytoskeletal dynamics and cellular tension
J. Parsons (2010)
Cellular Motility Driven by Assembly and Disassembly of Actin Filaments
T. Pollard (2003)
The distribution of secondary growths in cancer of the breast. 1889.
S. Paget (1989)
Force Measurements of the a 5 b 1 Integrin-Fibronectin Interaction
F. Li (2003)
Tumor Suppressor PTEN Mediates Sensing of Chemoattractant Gradients
M. Iijima (2002)
In vivo phage display and vascular heterogeneity: implications for targeted medicine.
M. Trepel (2002)
Interstitial flow and its effects in soft tissues.
M. Swartz (2007)
Letter: Lower oesophageal sphincter.
Bingham Ja (1974)
Selectin Ligand Expression Regulates the Initial Vascular Interactions of Colon Carcinoma Cells
Susan L Napier (2007)
Arrest and extravasation of B16 amelanotic melanoma in murine lungs. A light and electron microscopic study.
J. Crissman (1985)
Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells.
J. Palumbo (2005)
Measurement of mechanical tractions exerted by cells in three-dimensional matrices
Wesley R. Legant (2010)
Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates.
D. Yamazaki (2009)
Blood viscosity, mass transport, and thrombogenesis.
Turitto Vt (1982)
Integrins Bidirectional, Allosteric Signaling Machines
R. Hynes (2002)
J. Cell Sci
Coexpression of Arp2 and WAVE2 predicts poor outcome in invasive breast carcinoma
K. Iwaya (2007)
PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
J. Li (1997)
Electrochemical release of fluorescently labeled thiols from patterned gold surfaces.
Tammer Ghaly (2010)
Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis
L. Borsig (2001)
Localised and reversible TGFβ signalling switches breast cancer cells from cohesive to single cell motility
S. Giampieri (2009)
Mechanics of single cells: rheology, time dependence, and fluctuations.
G. Massiera (2007)
This paper is referenced by
Physical Mechanisms and High-Throughput Imaging of Tumor Cell Migration in Confining Microenvironments
Colin D. Paul (2015)
Decreased expression of DUSP4 is associated with liver and lung metastases in colorectal cancer
Susumu SaigusaYasuhiro (2013)
Effects of hemodynamic shear stress on circulating tumor cells
Yunhan How (2014)
Feedback regulation loop between bonemorphogenetic proteins and theirantagonists in prostate cancer and theimplication in bone metastasis
Jeyna Resaul (2018)
The Mechanism Responsible For Mechanically Enhanced Cancer Cell Invasion
Alexander N. Gasparski (2018)
Microfluidic Analysis for Separating and Measuring the Deformability of Cancer Cell Subpopulations
Yanan Chang (2019)
Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma
D. Tang (2013)
Cancer cell motility: lessons from migration in confined spaces
C. Paul (2017)
Cancer Stem Cells in Metastasis Therapy.
Esra Aydemir Çoban (2018)
Ninjurin1 suppresses metastatic property of lung cancer cells through inhibition of interleukin 6 signaling pathway
Yeongsu Jang (2016)
Modified cantilever arrays improve sensitivity and reproducibility of nanomechanical sensing in living cells
Samadhan B. Patil (2018)
Circulating tumor cells: utopia or reality?
V. Conteduca (2013)
Computational analysis of adhesion between a cancer cell and a white blood cell in a bifurcated microvessel
A. Khorram (2020)
Mechanochemistry in cancer cell metastasis
D. Zhang (2019)
An allometric approach of tumor-angiogenesis.
O. Szász (2018)
Defective membrane repair machinery impairs survival of invasive cancer cells
F. Bouvet (2020)
Decreased expression of DUSP4 is associated with liver and lung metastases in colorectal cancer
S. Saigusa (2013)
Mechanosensitive ion channels push cancer progression.
Zoltán Pethő (2019)
Characterization and Separation of Cancer Cells with a Wicking Fiber Device
S. Tabbaa (2017)
Statistical analysis of cell migration in 3D using the anisotropic persistent random walk model
Pei-Hsun Wu (2015)
Using Integrated Cancer-on-Chip Platforms to Emulate and Probe Various Cancer Models
Ziqiu Tong (2019)
High-Resolution Traction Force Microscopy 20
S. Plotnikov (2014)
Mismatch in mechanical and adhesive properties induces pulsating cancer cell migration in epithelial monolayer.
Meng-Horng Lee (2012)
Following MicroRNAs Through the Cancer Metastatic Cascade.
Eleonora Grisard (2017)
Characterizing cellular mechanical phenotypes with mechano-node-pore sensing
Junghyun Kim (2018)
Microenvironmental Stiffness of 3D Polymeric Structures to Study Invasive Rates of Cancer Cells
E. D. Lemma (2017)
Collective dynamics of cancer cells confined in a confluent monolayer of normal cells.
Shao-Zhen Lin (2017)
Role of Mechanotransduction and Tension in T Cell Function
Jérémie Rossy (2018)
The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen
Betty Luong (2018)
The Physics of Cancer
C. L. Porta (2017)
Abstract 3766: Mechanical properties of cancer cells: a possible biomarker for stemness.
Ameneh Mohammadalipour (2013)
Computational modeling and simulation of cellular growth and migration in angiogenesis
Johannes Florian Milde (2013)See more