Biomechanical regulation of cell orientation and fate

Biomechanical regulation of tumor phenotypes have been noted for several decades, yet the function of mechanics in the co-evolution of the tumor epithelium and altered cancer extracellular matrix has not been appreciated until fairly recently. In this review, we examine the dynamic interaction between the developing epithelia and the extracellular matrix, and discuss how similar interactions are exploited by the genetically modified epithelium during tumor progression. We emphasize the process of mechanoreciprocity, which is a phenomenon observed during epithelial transformation, in which tension generated within the extracellular microenvironment induce and cooperate with opposing reactive forces within transformed epithelium to drive tumor progression and metastasis. We highlight the importance of matrix remodeling, and present a new, emerging paradigm that underscores the importance of tissue morphology as a key regulator of epithelial cell invasion and metastasis.

[1]  Joyce Y. Wong,et al.  Directed Movement of Vascular Smooth Muscle Cells on Gradient-Compliant Hydrogels† , 2003 .

[2]  G. Giannelli,et al.  Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. , 1997, Science.

[3]  Zena Werb,et al.  Stromal Effects on Mammary Gland Development and Breast Cancer , 2002, Science.

[4]  B. Nebe,et al.  Stimulation of integrin receptors using a magnetic drag force device induces an intracellular free calcium response. , 1996, European journal of cell biology.

[5]  Jayanta Debnath,et al.  Modeling morphogenesis and oncogenesis in three-dimensional breast epithelial cultures. , 2008, Annual review of pathology.

[6]  Richard O. Hynes,et al.  Integrin-mediated Signals Regulated by Members of the Rho Family of GTPases , 1998, The Journal of cell biology.

[7]  V. Weaver,et al.  Tumour-stromal interactions: Integrins and cell adhesions as modulators of mammary cell survival and transformation , 2001, Breast Cancer Research.

[8]  C. Watson Key stages in mammary gland development - Involution: apoptosis and tissue remodelling that convert the mammary gland from milk factory to a quiescent organ , 2006, Breast Cancer Research.

[9]  P. Davies,et al.  Flow-mediated endothelial mechanotransduction. , 1995, Physiological reviews.

[10]  M. Bissell,et al.  Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Jain,et al.  Lack of telopeptides in fibrillar collagen I promotes the invasion of a metastatic breast tumor cell line. , 2005, Cancer research.

[12]  P. Janmey,et al.  Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. , 2005, Cell motility and the cytoskeleton.

[13]  Jennifer L West,et al.  Photocrosslinkable polyvinyl alcohol hydrogels that can be modified with cell adhesion peptides for use in tissue engineering. , 2002, Biomaterials.

[14]  J. Saklatvala,et al.  FGF-2 is bound to perlecan in the pericellular matrix of articular cartilage, where it acts as a chondrocyte mechanotransducer. , 2007, Osteoarthritis and cartilage.

[15]  P. Weinhold,et al.  Comparison of cellular strain with applied substrate strain in vitro. , 2007, Journal of biomechanics.

[16]  Richard T. Lee,et al.  Cell mechanics and mechanotransduction: pathways, probes, and physiology. , 2004, American journal of physiology. Cell physiology.

[17]  C. S. Chen,et al.  Geometric control of cell life and death. , 1997, Science.

[18]  Jens Friedrichs,et al.  Cellular remodelling of individual collagen fibrils visualized by time-lapse AFM. , 2007, Journal of molecular biology.

[19]  B. Hinz,et al.  Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix , 2007, The Journal of cell biology.

[20]  Micah Dembo,et al.  Mammary epithelial cell: influence of extracellular matrix composition and organization during development and tumorigenesis. , 2007, The international journal of biochemistry & cell biology.

[21]  Emilio Hirsch,et al.  Integrin signalling: the tug-of-war in heart hypertrophy. , 2006, Cardiovascular research.

[22]  Paolo A. Netti,et al.  Solid stress inhibits the growth of multicellular tumor spheroids , 1997, Nature Biotechnology.

[23]  E. Rodriguez-Boulan,et al.  Assembly of enveloped viruses in Madin-Darby canine kidney cells: polarized budding from single attached cells and from clusters of cells in suspension , 1983, The Journal of cell biology.

[24]  Richard G. W. Anderson,et al.  Integrins Regulate Rac Targeting by Internalization of Membrane Domains , 2004, Science.

[25]  D. Plewes,et al.  Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples , 2007, Physics in medicine and biology.

[26]  B. Willis,et al.  TGF-β-induced EMT: mechanisms and implications for fibrotic lung disease , 2007 .

[27]  G. Schmid-Schönbein,et al.  Regulation of CD18 expression on neutrophils in response to fluid shear stress , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[28]  T. Quinn,et al.  Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells. , 2002, American journal of physiology. Lung cellular and molecular physiology.

[29]  Andrés J. García,et al.  Oscillatory tension differentially modulates matrix metabolism and cytoskeletal organization in chondrocytes and fibrochondrocytes. , 2004, Journal of biomechanics.

[30]  John S. Condeelis,et al.  ROCK- and Myosin-Dependent Matrix Deformation Enables Protease-Independent Tumor-Cell Invasion In Vivo , 2006, Current Biology.

[31]  J. Reichelt Mechanotransduction of keratinocytes in culture and in the epidermis. , 2007, European journal of cell biology.

[32]  C. Larabell,et al.  Reversion of the Malignant Phenotype of Human Breast Cells in Three-Dimensional Culture and In Vivo by Integrin Blocking Antibodies , 1997, The Journal of cell biology.

[33]  Micah Dembo,et al.  Focal adhesion kinase is involved in mechanosensing during fibroblast migration , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[34]  D. I. Wang,et al.  Experimental Collision Efficiencies of Polymer‐Flocculated Animal Cells , 1990, Biotechnology progress.

[35]  J. Segall,et al.  Intravital imaging of cell movement in tumours , 2003, Nature Reviews Cancer.

[36]  Ray Keller,et al.  How we are shaped: the biomechanics of gastrulation. , 2003, Differentiation; research in biological diversity.

[37]  W J Nelson,et al.  Steps in the morphogenesis of a polarized epithelium. I. Uncoupling the roles of cell-cell and cell-substratum contact in establishing plasma membrane polarity in multicellular epithelial (MDCK) cysts. , 1990, Journal of cell science.

[38]  Ricardo Garcia,et al.  Nanoscale compositional mapping with gentle forces. , 2007, Nature materials.

[39]  H. Kleinman,et al.  Role of the extracellular matrix in morphogenesis. , 2003, Current opinion in biotechnology.

[40]  W J Nelson,et al.  Steps in the morphogenesis of a polarized epithelium. II. Disassembly and assembly of plasma membrane domains during reversal of epithelial cell polarity in multicellular epithelial (MDCK) cysts. , 1990, Journal of cell science.

[41]  M. Stella,et al.  Release and activation of matrix metalloproteinase-9 during in vitro mechanical compression in hypertrophic scars. , 2002, Archives of dermatology.

[42]  M J Bissell,et al.  How does the extracellular matrix direct gene expression? , 1982, Journal of theoretical biology.

[43]  Cynthia A. Reinhart-King,et al.  Tensional homeostasis and the malignant phenotype. , 2005, Cancer cell.

[44]  D. Ingber,et al.  A possible mechanism for inhibition of angiogenesis by angiostatic steroids: induction of capillary basement membrane dissolution. , 1986, Endocrinology.

[45]  Matthew J. Paszek,et al.  The Tension Mounts: Mechanics Meets Morphogenesis and Malignancy , 2004, Journal of Mammary Gland Biology and Neoplasia.

[46]  M. Hendrix,et al.  Paradoxical roles for lysyl oxidases in cancer—A prospect , 2007, Journal of cellular biochemistry.

[47]  R. Hochmuth,et al.  Micropipette aspiration of living cells. , 2000, Journal of biomechanics.

[48]  J. Lü,et al.  Regulation of early lung morphogenesis: questions, facts and controversies , 2006, Development.

[49]  J. Pollard,et al.  Macrophages promote collagen fibrillogenesis around terminal end buds of the developing mammary gland , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[50]  M. Dembo,et al.  Cell movement is guided by the rigidity of the substrate. , 2000, Biophysical journal.

[51]  I. M. Neiman,et al.  [Inflammation and cancer]. , 1974, Patologicheskaia fiziologiia i eksperimental'naia terapiia.

[52]  M. Hendrix,et al.  A molecular role for lysyl oxidase in breast cancer invasion. , 2002, Cancer research.

[53]  Jayanta Debnath,et al.  Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. , 2003, Methods.

[54]  P. Sommer,et al.  Lysyl oxidase-like protein localizes to sites of de novo fibrinogenesis in fibrosis and in the early stromal reaction of ductal breast carcinomas. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[55]  A. Huttenlocher,et al.  Integrin-mediated adhesion regulates cell polarity and membrane protrusion through the Rho family of GTPases. , 2001, Molecular biology of the cell.

[56]  Y. Wang,et al.  Cell locomotion and focal adhesions are regulated by substrate flexibility. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[57]  D. Discher,et al.  Matrix Elasticity, Cytoskeletal Tension, and TGF-β: The Insoluble and Soluble Meet , 2008, Science Signaling.

[58]  M. Stella,et al.  Effect of in vitro mechanical compression on Epilysin (matrix metalloproteinase‐28) expression in hypertrophic scars , 2005, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[59]  G. Robinson,et al.  Cooperation of signalling pathways in embryonic mammary gland development , 2008, Nature Reviews Genetics.

[60]  Rakesh K. Jain,et al.  Pathology: Cancer cells compress intratumour vessels , 2004, Nature.

[61]  E. Grigorieva,et al.  Expression of different proteoglycans in human breast tumors , 2007, Biochemistry (Moscow).

[62]  F. Silver,et al.  Mechanosensing and mechanochemical transduction: how is mechanical energy sensed and converted into chemical energy in an extracellular matrix? , 2003, Critical reviews in biomedical engineering.

[63]  Effects of Compressive Loading on Human Synovium-derived Cells , 2007, Journal of dental research.

[64]  V. Weaver,et al.  Tissue structure, nuclear organization, and gene expression in normal and malignant breast. , 1999, Cancer research.

[65]  M J Bissell,et al.  Extracellular matrix signaling from the cellular membrane skeleton to the nuclear skeleton: a model of gene regulation. , 1996, Recent progress in hormone research.

[66]  George Oster,et al.  Force generation by actin polymerization II: the elastic ratchet and tethered filaments. , 2003, Biophysical journal.

[67]  Douglas W DeSimone,et al.  Cell adhesion receptors in mechanotransduction. , 2008, Current opinion in cell biology.

[68]  M. Dembo,et al.  Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts. , 2001, Biophysical journal.

[69]  C. López-Otín,et al.  Emerging roles of proteases in tumour suppression , 2007, Nature Reviews Cancer.

[70]  M J Bissell,et al.  Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane. , 1989, Development.

[71]  Genee Y. Lee,et al.  The morphologies of breast cancer cell lines in three‐dimensional assays correlate with their profiles of gene expression , 2007, Molecular oncology.

[72]  K. J. Grande-Allen,et al.  Effects of static and cyclic loading in regulating extracellular matrix synthesis by cardiovascular cells. , 2006, Cardiovascular research.

[73]  Keith E. Mostov,et al.  Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly , 2001, Nature Cell Biology.

[74]  H. Langberg,et al.  Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types , 2007, The Journal of physiology.

[75]  Peter H Watson,et al.  Mammographic density is related to stroma and stromal proteoglycan expression , 2003, Breast Cancer Research.

[76]  A. Strongin,et al.  Mislocalization and unconventional functions of cellular MMPs in cancer , 2006, Cancer and Metastasis Reviews.

[77]  V. Weaver,et al.  The tissue microenvironment as an epigenetic tumor modifier. , 2003, Methods in molecular biology.

[78]  Stephen W Byers,et al.  New rules for feedlots. , 1998, Environmental health perspectives.

[79]  Valerie M. Weaver,et al.  A tense situation: forcing tumour progression , 2009, Nature Reviews Cancer.

[80]  John A. Pedersen,et al.  Mechanobiology in the Third Dimension , 2005, Annals of Biomedical Engineering.

[81]  S. Leivonen,et al.  Transforming growth factor‐β signaling in cancer invasion and metastasis , 2007, International journal of cancer.

[82]  E. Farge Mechanical Induction of Twist in the Drosophila Foregut/Stomodeal Primordium , 2003, Current Biology.

[83]  A. White,et al.  A biomechanical comparison of the effects of constant and cyclic compression on fracture healing in rabbit long bones. , 1979, Acta orthopaedica Scandinavica.

[84]  O. Hamill,et al.  Molecular basis of mechanotransduction in living cells. , 2001, Physiological reviews.

[85]  Andrew J. Ewald,et al.  Matrix metalloproteinases and the regulation of tissue remodelling , 2007, Nature Reviews Molecular Cell Biology.

[86]  Y. Gan Invited review article: a review of techniques for attaching micro- and nanoparticles to a probe's tip for surface force and near-field optical measurements. , 2007, The Review of scientific instruments.

[87]  Kenneth M. Yamada,et al.  The matrix reorganized: extracellular matrix remodeling and integrin signaling. , 2006, Current opinion in cell biology.

[88]  Clare M Waterman,et al.  High resolution traction force microscopy based on experimental and computational advances. , 2008, Biophysical journal.

[89]  S. Leivonen,et al.  Transforming growth factor-beta signaling in cancer invasion and metastasis. , 2007, International journal of cancer.

[90]  J. Erler,et al.  Lysyl oxidase mediates hypoxic control of metastasis. , 2006, Cancer research.

[91]  Joseph Khoury,et al.  Signaling through PI3K/Akt mediates stretch and PDGF-BB-dependent DNA synthesis in bladder smooth muscle cells. , 2003, The Journal of urology.

[92]  R. Adam,et al.  Cyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells. , 2000, American journal of physiology. Cell physiology.

[93]  Donald E Ingber,et al.  Control of basement membrane remodeling and epithelial branching morphogenesis in embryonic lung by Rho and cytoskeletal tension , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[94]  M. Bissell,et al.  Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. , 2006, Annual review of cell and developmental biology.

[95]  A. Grodzinsky,et al.  Cartilage tissue remodeling in response to mechanical forces. , 2000, Annual review of biomedical engineering.

[96]  Shouren Ge,et al.  Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties. , 2007, Biomaterials.

[97]  Yasuhiro Sawada,et al.  Activation of a signaling cascade by cytoskeleton stretch. , 2004, Developmental cell.

[98]  R. Stern Hyaluronidases in cancer biology. , 2008, Seminars in cancer biology.

[99]  K. Campbell,et al.  A role for dystroglycan in epithelial polarization: loss of function in breast tumor cells. , 2002, Cancer research.

[100]  Ning Wang,et al.  Caldesmon-dependent switching between capillary endothelial cell growth and apoptosis through modulation of cell shape and contractility , 2004, Angiogenesis.

[101]  B. Willis,et al.  TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. , 2007, American journal of physiology. Lung cellular and molecular physiology.

[102]  Daniel Choquet,et al.  Extracellular Matrix Rigidity Causes Strengthening of Integrin–Cytoskeleton Linkages , 1997, Cell.

[103]  Donald E Ingber,et al.  Extracellular matrix controls myosin light chain phosphorylation and cell contractility through modulation of cell shape and cytoskeletal prestress. , 2004, American journal of physiology. Cell physiology.

[104]  M. Chiquet,et al.  Gene regulation by mechanotransduction in fibroblasts. , 2007, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[105]  Melody A Swartz,et al.  A driving force for change: interstitial flow as a morphoregulator. , 2007, Trends in cell biology.

[106]  J. Emerman,et al.  Maintenance and induction of morphological differentiation in dissociated mammary epithelium on floating collagen membranes , 1977, In Vitro.

[107]  I. Leivo Structure and composition of early basement membranes: studies with early embryos and teratocarcinoma cells. , 1983, Medical biology.

[108]  S. Scherer,et al.  Epigenetic Regulation of HYAL-1 Hyaluronidase Expression , 2008, Journal of Biological Chemistry.

[109]  Jason W. Triplett,et al.  Mechanical loading by fluid shear stress enhances IGF-1 receptor signaling in osteoblasts in a PKCzeta-dependent manner. , 2007, Molecular & cellular biomechanics : MCB.

[110]  K. Beningo,et al.  Flexible substrata for the detection of cellular traction forces. , 2002, Trends in cell biology.

[111]  M. Schwartz,et al.  Integrins in Mechanotransduction* , 2004, Journal of Biological Chemistry.

[112]  M J Bissell,et al.  The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. , 2001, Development.

[113]  T. Naoe,et al.  Integrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch* , 2005, Journal of Biological Chemistry.

[114]  一宮 久之 Compressive mechanical stress promotes osteoclast formation through RANKL expression on synovial cells , 2006 .

[115]  B. Verrier,et al.  Polarity reversal of inside‐out thyroid follicles cultured within collagen gel: reexpression of specific functions , 1984, Biology of the cell.

[116]  M J Bissell,et al.  The development of a functionally relevant cell culture model of progressive human breast cancer. , 1995, Seminars in cancer biology.

[117]  K. Volokh,et al.  Stresses in growing soft tissues. , 2006, Acta biomaterialia.

[118]  Mina J. Bissell The organizing principle: microenvironmental influences in the normal and malignant breast , 2010 .

[119]  J. H. Wang,et al.  An Introductory Review of Cell Mechanobiology , 2006, Biomechanics and modeling in mechanobiology.

[120]  Z. Werb,et al.  Hormonal and local control of mammary branching morphogenesis. , 2006, Differentiation; research in biological diversity.

[121]  Mina J Bissell,et al.  Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. , 2010, Journal of cell science.

[122]  Z. Werb,et al.  New functions for the matrix metalloproteinases in cancer progression , 2002, Nature Reviews Cancer.

[123]  M. Neeman,et al.  Lysyl oxidase-related protein-1 promotes tumor fibrosis and tumor progression in vivo. , 2003, Cancer research.