Skip to main content

Advertisement

SpringerLink
Log in

The Tension Mounts: Mechanics Meets Morphogenesis and Malignancy

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

The tissue microenvironment regulates mammary gland development and tissue homeostasis through soluble, insoluble and cellular cues that operate within the three dimensional architecture of the gland. Disruption of these critical cues and loss of tissue architecture characterize breast tumors. The developing and lactating mammary gland are also subject to a plethora of tensional forces that shape the morphology of the gland and orchestrate its functionally differentiated state. Moreover, malignant transformation of the breast is associated with dramatic changes in gland tension that include elevated compression forces, high tensional resistance stresses and increased extracellular matrix stiffness. Chronically increased mammary gland tension may influence tumor growth, perturb tissue morphogenesis, facilitate tumor invasion, and alter tumor survival and treatment responsiveness. Because mammary tissue differentiation is compromised by high mechanical force and transformed cells exhibit altered mechanoresponsiveness, malignant transformation of the breast may be functionally linked to perturbed tensional-homeostasis. Accordingly, it will be important to define the role of tensional force in mammary gland development and tumorigenesis. Additionally, it will be critical to identify the key molecular elements regulating tensional-homeostasis of the mammary gland and thereafter to characterize their associated mechanotransduction pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Radisky D, Hagios C, Bissell MJ. Tumors are unique organs defined by abnormal signaling and context. Semin Cancer Biol 2001;11(2):87–95.

    Google Scholar 

  2. Dickson C, Spencer-Dene B, Dillon C, Fantl V. Tyrosine kinase signalling in breast cancer: Fibroblast growth factors and their receptors. Breast Cancer Res 2000;2(3):191–6.

    Google Scholar 

  3. Casalini P, Iorio MV, Galmozzi E, Menard S. Role of HER receptors family in development and differentiation. J Cell Physiol 2004;200(3):343–50.

    Google Scholar 

  4. Fata JE, Werb Z, Bissell MJ. Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes. Breast Cancer Res 2004;6(1):1–11.

    Google Scholar 

  5. Wiseman BS, Werb Z. Stromal effects on mammary gland development and breast cancer. Science 2002;296(5570):1046–9.

    Google Scholar 

  6. Sternlicht MD, Lochter A, Sympson CJ, Huey B, Rougier JP, Gray JW, et al. The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 1999;98(2):137–46.

    Google Scholar 

  7. Weaver VM, Petersen OW, Wang F, Larabell CA, Briand P, Damsky C, et al. Reversion of the malignant phenotype of human breast cells in three- dimensional culture and in vivo by integrin blocking antibodies. J Cell Biol 1997;137(1):231–45.

    Google Scholar 

  8. White DE, Kurpios NA, Zuo D, Hassell JA, Blaess S, Mueller U, et al. Targeted disruption of beta1-integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction. Cancer Cell 2004;6(2):159–70.

    Google Scholar 

  9. Czirok A, Rongish BJ, Little CD. Extracellular matrix dynamics during vertebrate axis formation. Dev Biol 2004;268(1):111–22.

    Google Scholar 

  10. Beloussov LV, Lakirev AV, Naumidi, II, Novoselov VV. Effects of relaxation of mechanical tensions upon the early morphogenesis of Xenopus laevis embryos. Int J Dev Biol 1990;34(4):409–19.

    Google Scholar 

  11. Ingber DE. Mechanobiology and diseases of mechanotransduction. Ann Med 2003;35(8):564–77.

    Google Scholar 

  12. Krouskop TA, Wheeler TM, Kallel F, Garra BS, Hall T. Elastic moduli of breast and prostate tissues under compression. Ultrason Imaging 1998;20(4):260–74.

    Google Scholar 

  13. Plewes DB, Bishop J, Samani A, Sciarretta J. Visualization and quantification of breast cancer biomechanical properties with magnetic resonance elastography. Phys Med Biol 2000;45(6):1591–610.

    Google Scholar 

  14. Emerman JT, Pitelka DR. Maintenance and induction of morphological differentiation in dissociated mammary epithelium on floating collagen membranes. In Vitro 1977;13(5):316–28.

    Google Scholar 

  15. Roskelley CD, Srebrow A, Bissell MJ. A hierarchy of ECM-mediated signalling regulates tissue-specific gene expression. Curr Opin Cell Biol 1995;7(5):736–47.

    Google Scholar 

  16. Wang HB, Dembo M, Wang YL. Substrate flexibility regulates growth and apoptosis of normal but not transformed cells. Am J Physiol-Cell Physiol 2000;279(5):C1345–50.

    Google Scholar 

  17. Wozniak MA, Desai R, Solski PA, Der CJ, Keely PJ. ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix. J Cell Biol 2003;163(3):583–95.

    Google Scholar 

  18. Bissell MJ, Hall HG, Parry G. How does the extracellular matrix direct gene expression? J Theor Biol 1982;99:31–68.

    Google Scholar 

  19. Oster GF, Murray JD, Harris AK. Mechanical aspects of mesenchymal morphogenesis. J Embryol Exp Morphol 1983;78:83–125.

    Google Scholar 

  20. Trinkaus J. Cells in organs. The forces that shape the embryo. 2nd ed. Englewood Cliffs (NJ): Prentice-Hall; 1984.

    Google Scholar 

  21. Wilkin MB, Becker MN, Mulvey D, Phan I, Chao A, Cooper K, et al. Drosophila dumpy is a gigantic extracellular protein required to maintain tension at epidermal-cuticle attachment sites. Curr Biol 2000;10(10):559–67.

    Google Scholar 

  22. Farge E. Mechanical induction of Twist in the Drosophila foregut/stomodeal primordium. Curr Biol 2003;13(16):1365–77.

    Google Scholar 

  23. Keller R, Davidson LA, Shook DR. How we are shaped: the biomechanics of gastrulation. Differentiation 2003;71(3):171–205.

    Google Scholar 

  24. Chu EY, Hens J, Andl T, Kairo A, Yamaguchi TP, Brisken C, et al. Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development 2004;131(19):4819–29.

    Google Scholar 

  25. Howard JC, Varallo VM, Ross DC, Roth JH, Faber KJ, Alman B, et al. Elevated levels of beta-catenin and fibronectin in three-dimensional collagen cultures of Dupuytren’s disease cells are regulated by tension in vitro. BMC Musculoskelet Disord 2003;4(1):16.

    Google Scholar 

  26. Fleury V, Watanabe T. Morphogenesis of fingers and branched organs: How collagen and fibroblasts break the symmetry of growing biological tissue. C R Biol 2002;325(5):571–83.

    Google Scholar 

  27. Lubkin SR, Li Z. Force and deformation on branching rudiments: Cleaving between hypotheses. Biomech Model Mechanobiol 2002;1(1):5–16.

    Google Scholar 

  28. Forgacs G. Surface tension and viscoelastic properties of embryonic tissues depend on the cytoskeleton. Biol Bull 1998;194(3):328–29; discussion 329–30.

    Google Scholar 

  29. Moore KA, Huang S, Kong Y, Sunday ME, Ingber DE. Control of embryonic lung branching morphogenesis by the Rho activator, cytotoxic necrotizing factor 1. J Surg Res 2002;104(2):95–100.

    Google Scholar 

  30. Miao H, Nickel CH, Cantley LG, Bruggeman LA, Bennardo LN, Wang B. EphA kinase activation regulates HGF-induced epithelial branching morphogenesis. J Cell Biol 2003;162(7):1281–92.

    Google Scholar 

  31. Barcellos-Hoff MH, Aggeler J, Ram TG, Bissell MJ. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane. Development 1989;105(2):223–35.

    Google Scholar 

  32. Weaver V, Bissell M. Functional culture models to study mechanisms governing apoptosis in normal and malignant mammary epithelial cells. J Mammary Gland Biol Neoplasia 1999;4(2):193–201.

    Google Scholar 

  33. Bross S, Braun PM, Michel MS, Juenemann KP, Alken P. Bladder wall tension during physiological voiding and in patients with an unstable detrusor or bladder outlet obstruction. BJU Int 2003;92(6):584–8.

    Google Scholar 

  34. Gunst SJ, Tang DD. The contractile apparatus and mechanical properties of airway smooth muscle. Eur Respir J 2000;15(3):600–16.

    Google Scholar 

  35. Lund LR, Romer J, Thomasset N, Solberg H, Pyke C, Bissell MJ, et al. Two distinct phases of apoptosis in mammary gland involution: Proteinase-independent and -dependent pathways. Development 1996;122(1):181–93.

    Google Scholar 

  36. Shamay A, Shapiro F, Mabjeesh SJ, Silanikove N. Casein-derived phosphopeptides disrupt tight junction integrity, and precipitously dry up milk secretion in goats. Life Sci 2002;70(23):2707–19.

    Google Scholar 

  37. Marti A, Feng Z, Altermatt HJ, Jaggi R. Milk accumulation triggers apoptosis of mammary epithelial cells. Eur J Cell Biol 1997;73(2):158–65.

    Google Scholar 

  38. Roose T, Netti PA, Munn LL, Boucher Y, Jain RK. Solid stress generated by spheroid growth estimated using a linear poroelasticity model small star, filled. Microvasc Res 2003;66(3):204–12.

    Google Scholar 

  39. Harris AL. Hypoxia—A key regulatory factor in tumour growth. Nat Rev Cancer 2002;2(1):38–47.

    Google Scholar 

  40. Shannon AM, Bouchier-Hayes DJ, Condron CM, Toomey D. Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev 2003;29(4):297–307.

    Google Scholar 

  41. Jain RK. Transport of molecules, particles, and cells in solid tumors. Annu Rev Biomed Eng 1999;1:241–63.

    Google Scholar 

  42. Padera TP, Stoll BR, Tooredman JB, Capen D, di Tomaso E, Jain RK. Pathology: cancer cells compress intratumour vessels. Nature 2004;427(6976):695.

    Google Scholar 

  43. Vincent TL, Hermansson MA, Hansen UN, Amis AA, Saklatvala J. Basic fibroblast growth factor mediates transduction of mechanical signals when articular cartilage is loaded. Arthritis Rheum 2004;50(2):526–33.

    Google Scholar 

  44. Quinn TP, Schlueter M, Soifer SJ, Gutierrez JA. Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2002;282(5):L897–903.

    Google Scholar 

  45. Adam RM, Roth JA, Cheng HL, Rice DC, Khoury J, Bauer SB, et al. Signaling through PI3K/Akt mediates stretch and PDGF-BB-dependent DNA synthesis in bladder smooth muscle cells. J Urol 2003;169(6):2388–93.

    Google Scholar 

  46. Reno F, Grazianetti P, Stella M, Magliacani G, Pezzuto C, Cannas M. Release and activation of matrix metalloproteinase-9 during in vitro mechanical compression in hypertrophic scars. Arch Dermatol 2002;138(4):475–8.

    Google Scholar 

  47. Ravikumar R, Flora G, Geddes JW, Hennig B, Toborek M. Nicotine attenuates oxidative stress, activation of redox-regulated transcription factors and induction of proinflammatory genes in compressive spinal cord trauma. Brain Res Mol Brain Res 2004;124(2):188–98.

    Google Scholar 

  48. Dennerll TJ, Joshi HC, Steel VL, Buxbaum RE, Heidemann SR. Tension and compression in the cytoskeleton of PC-12 neurites. II: Quantitative measurements. J Cell Biol 1988;107(2):665–74.

    Google Scholar 

  49. Tschumperlin DJ, Shively JD, Kikuchi T, Drazen JM. Mechanical stress triggers selective release of fibrotic mediators from bronchial epithelium. Am J Respir Cell Mol Biol 2003;28(2):142–9.

    Google Scholar 

  50. Oft M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E. TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Gene Dev 1996;10(19):2462–77.

    Google Scholar 

  51. Miettinen PJ, Ebner R, Lopez AR, Derynck R. TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: Involvement of type I receptors. J Cell Biol 1994;127(6 Pt 2):2021–36.

    Google Scholar 

  52. Hosobuchi M, Stampfer MR. Effects of transforming growth factor beta on growth of human mammary epithelial cells in culture. In Vitro Cell Dev Biol 1989;25(8):705–13.

    Google Scholar 

  53. Akhurst RJ, Derynck R. TGF-beta signaling in cancer—A double-edged sword. Trends Cell Biol 2001;11(11):S44–51.

    Google Scholar 

  54. Huang H, Kamm RD, Lee RT. Cell mechanics and mechanotransduction: Pathways, probes, and physiology. Am J Physiol Cell Physiol 2004;287(1):C1–11.

    Google Scholar 

  55. Janmey PA, Weitz DA. Dealing with mechanics: Mechanisms of force transduction in cells. Trends Biochem Sci 2004;29(7):364–70.

    Google Scholar 

  56. Tschumperlin DJ, Dai G, Maly IV, Kikuchi T, Laiho LH, McVittie AK, et al. Mechanotransduction through growth-factor shedding into the extracellular space. Nature 2004;429(6987):83–6.

    Google Scholar 

  57. Katsumi A, Orr AW, Tzima E, Schwartz MA. Integrins in mechanotransduction. J Biol Chem 2004;279(13):12001–4.

    Google Scholar 

  58. Carrion-Vazquez M, Oberhauser AF, Fowler SB, Marszalek PE, Broedel SE, Clarke J, et al. Mechanical and chemical unfolding of a single protein: A comparison. Proc Natl Acad Sci USA 1999;96(7):3694–9.

    Google Scholar 

  59. Gilmore AP, Burridge K. Cell adhesion. Cryptic sites in vinculin. Nature 1995;373(6511):197.

    Google Scholar 

  60. Hamill OP, Martinac B. Molecular basis of mechanotransduction in living cells. Physiol Rev 2001;81(2):685–740.

    Google Scholar 

  61. Helmke BP, Davies PF. The cytoskeleton under external fluid mechanical forces: Hemodynamic forces acting on the endothelium. Ann Biomed Eng 2002;30(3):284–96.

    Google Scholar 

  62. Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev 1995;75(3):519–60.

    Google Scholar 

  63. Chen CS, Tan J, Tien J. Mechanotransduction at cell-matrix and cell-cell contacts. Annu Rev Biomed Eng 2004;6:275–302.

    Google Scholar 

  64. Lauffenburger DA, Horwitz AF. Cell migration: A physically integrated molecular process. Cell 1996;84(3):359–69.

    Google Scholar 

  65. Dembo M, Wang YL. Stresses at the cell-to-substrate interface during locomotion of fibroblasts. Biophys J 1999;76(4):2307–2316.

    Google Scholar 

  66. Matrisian LM. Cancer biology: Extracellular proteinases in malignancy. Curr Biol 1999;9(20):R776–8.

    Google Scholar 

  67. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420(6917):860–7.

    Google Scholar 

  68. Bissell MJ, Radisky D. Putting tumours in context. Nat Rev Cancer 2001;1(1):46–54.

    Google Scholar 

  69. Decitre M, Gleyzal C, Raccurt M, Peyrol S, Aubert-Foucher E, Csiszar K, 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. Lab Invest 1998;78(2):143–51.

    Google Scholar 

  70. McCawley LJ, Matrisian LM. Matrix metalloproteinases: They’re not just for matrix anymore! Curr Opin Cell Biol 2001;13(5):534–40.

    Google Scholar 

  71. Yeung T, Georges PC, Flanagan LA, Marg B, Ortiz M, Funaki M, Zahir N, Ming W, Weaver V, Janmey PA. Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motil Cytoskeleton 2005;60(1):24–34.

    Google Scholar 

  72. Gray DS, Tien J, Chen CS. Repositioning of cells by mechanotaxis on surfaces with micropatterned Young’s modulus. J Biomed Mater Res 2003;66A(3):605–14.

    Google Scholar 

  73. Munevar S, Wang YL, Dembo M. Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts. Biophys J 2001;80(4):1744–1757.

    Google Scholar 

  74. Lo CM, Buxton DB, Chua GC, Dembo M, Adelstein RS, Wang YL. Nonmuscle myosin IIb is involved in the guidance of fibroblast migration. Mol Biol Cell 2004;15(3):982–9.

    Google Scholar 

  75. Wang HB, Dembo M, Hanks SK, Wang Y. Focal adhesion kinase is involved in mechanosensing during fibroblast migration. Proc Natl Acad Sci USA 2001;98(20):11295–300.

    Google Scholar 

  76. Lo CM, Wang HB, Dembo M, Wang YL. Cell movement is guided by the rigidity of the substrate. Biophys J 2000;79(1):144–152.

    Google Scholar 

  77. Huang S, Ingber DE. The structural and mechanical complexity of cell-growth control. Nat Cell Biol 1999;1(5):E131–8.

    Google Scholar 

  78. Ebihara T, Venkatesan N, Tanaka R, Ludwig MS. Changes in extracellular matrix and tissue viscoelasticity in bleomycin-induced lung fibrosis. Temporal aspects. Am J Respir Crit Care Med 2000;162(4 Pt 1):1569–76.

    Google Scholar 

  79. Zahir N, Weaver VM. Death in the third dimension: apoptosis regulation and tissue architecture. Curr Opin Genet Dev 2004;14(1):71–80.

    Google Scholar 

  80. Weaver VM, Lelievre S, Lakins JN, Chrenek MA, Jones JC, Giancotti F, et al. Beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2002;2(3):205–16.

    Google Scholar 

  81. Epstein ND, Davis JS. Sensing stretch is fundamental. Cell 2003;112(2):147–50.

    Google Scholar 

  82. Gillespie PG, Walker RG. Molecular basis of mechanosensory transduction. Nature 2001;413(6852):194–202.

    Google Scholar 

  83. Sawada Y, Sheetz MP. Force transduction by Triton cytoskeletons. J Cell Biol 2002;156(4):609–15.

    Google Scholar 

  84. Galbraith CG, Yamada KM, Sheetz MP. The relationship between force and focal complex development. J Cell Biol 2002;159(4):695–705.

    Google Scholar 

  85. Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell surface and through the cytoskeleton. Science 1993;260(5111):1124–7.

    Google Scholar 

  86. Giannone G, Jiang G, Sutton DH, Critchley DR, Sheetz MP. Talin1 is critical for force-dependent reinforcement of initial integrin-cytoskeleton bonds but not tyrosine kinase activation. J Cell Biol 2003;163(2):409–19.

    Google Scholar 

  87. Chrenek MA, Wong P, Weaver VM. Tumour-stromal interactions. Integrins and cell adhesions as modulators of mammary cell survival and transformation. Breast Cancer Res 2001;3(4):224–9.

    Google Scholar 

  88. Zutter MM, Sun H, Santoro SA. Altered integrin expression and the malignant phenotype: the contribution of multiple integrated integrin receptors. J Mammary Gland Biol Neoplasia 1998;3(2):191–200.

    Google Scholar 

  89. Oktay MH, Oktay K, Hamele-Bena D, Buyuk A, Koss LG. Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas. Hum Pathol 2003;34(3):240–5.

    Google Scholar 

  90. Drury JL, Mooney DJ. Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials 2003;24(24):4337–51.

    Google Scholar 

  91. Davies PF. Multiple signaling pathways in flow-mediated endothelial mechano-transduction: PYK-ing the right location. Arterioscler Thromb Vasc Biol 2002;22(11):1755–7.

    Google Scholar 

  92. Barakat A, Lieu D. Differential responsiveness of vascular endothelial cells to different types of fluid mechanical shear stress. Cell Biochem Biophys 2003;38(3):323–43.

    Google Scholar 

  93. Ng CP, Swartz MA. Fibroblast alignment under interstitial fluid flow using a novel 3-D tissue culture model. Am J Physiol Heart Circ Physiol 2003;284(5):H1771–7.

    Google Scholar 

  94. Clerin V, Nichol JW, Petko M, Myung RJ, Gaynor JW, Gooch KJ. Tissue engineering of arteries by directed remodeling of intact arterial segments. Tissue Eng 2003;9(3):461–72.

    Google Scholar 

  95. Lee JH, Kisiday J, Grodzinsky AJ. Tissue-engineered versus native cartilage: linkage between cellular mechano-transduction and biomechanical properties. Novartis Found Symp 2003;249:52–64.

    Google Scholar 

  96. Grodzinsky AJ, Levenston ME, Jin M, Frank EH. Cartilage tissue remodeling in response to mechanical forces. Annu Rev Biomed Eng 2000;2:691–713.

    Google Scholar 

  97. Sikavitsas VI, Temenoff JS, Mikos AG. Biomaterials and bone mechanotransduction. Biomaterials 2001;22(19):2581–93.

    Google Scholar 

  98. Tschumperlin DJ, Oswari J, Margulies AS. Deformation-induced injury of alveolar epithelial cells. Effect of frequency, duration, and amplitude. Am J Respir Crit Care Med 2000;162(2 Pt 1):357–62.

    Google Scholar 

  99. Savel RH, Yao EC, Gropper MA. Protective effects of low tidal volume ventilation in a rabbit model of Pseudomonas aeruginosa-induced acute lung injury. Crit Care Med 2001;29(2):392–8.

    Google Scholar 

  100. Grinnell F. Fibroblast biology in three-dimensional collagen matrices. Trends Cell Biol 2003;13(5):264–9.

    Google Scholar 

  101. Elbjeirami WM, Yonter EO, Starcher BC, West JL. Enhancing mechanical properties of tissue-engineered constructs via lysyl oxidase crosslinking activity. J Biomed Mater Res 2003;66A(3):513–21.

    Google Scholar 

  102. Pelham RJ, Jr, Wang Y. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci USA 1997;94(25):13661–5.

    Google Scholar 

  103. Reinhart-King CA, Dembo M, Hammer DA. Endothelial Cell Traction Forces on RGD-Derivatized Polyacrylamide Substrata. Langmuir 2003;19:1573–1579.

    Google Scholar 

  104. Flanagan LA, Ju YE, Marg B, Osterfield M, Janmey PA. Neurite branching on deformable substrates. Neuroreport 2002;13(18):2411–5.

    Google Scholar 

  105. Engler AJ, Griffin MA, Sen S, Bonnemann CG, Sweeney HL, Discher DE. Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments. J Cell Biol 2004;166(6):877–87.

    Google Scholar 

  106. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 2004;6(4):483–95.

    Google Scholar 

  107. O’Brien LE, Zegers MM, Mostov KE. Opinion: Building epithelial architecture: insights from three- dimensional culture models. Nat Rev Mol Cell Biol 2002;3(7):531–7.

    Google Scholar 

  108. Schmedlen RH, Masters KS, West JL. Photocrosslinkable polyvinyl alcohol hydrogels that can be modified with cell adhesion peptides for use in tissue engineering. Biomaterials 2002;23(22):4325–32.

    Google Scholar 

  109. Kuo SC, Sheetz MP. Optical tweezers in cell biology. Trends Cell Biol 1992;2(4):116–8.

    Google Scholar 

  110. Choquet D, Felsenfeld DP, Sheetz MP. Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell 1997;88(1):39–48.

    Google Scholar 

  111. Riveline D, Zamir E, Balaban NQ, Schwarz US, Ishizaki T, Narumiya S, et al. Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J Cell Biol 2001;153(6):1175–86.

    Google Scholar 

  112. Tan JL, Tien J, Pirone DM, Gray DS, Bhadriraju K, Chen CS. Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc Natl Acad Sci USA 2003;100(4):1484–9.

    Google Scholar 

  113. Balaban NQ, Schwarz US, Riveline D, Goichberg P, Tzur G, Sabanay I, et al. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat Cell Biol 2001;3(5):466–472.

    Google Scholar 

  114. Katz BZ, Zamir E, Bershadsky A, Kam Z, Yamada KM, Geiger B. Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions. Mol Biol Cell 2000;11(3):1047–60.

    Google Scholar 

  115. Bissell MJ, Radisky DC, Rizki A, Weaver VM, Petersen OW. The organizing principle: Microenvironmental influences in the normal and malignant breast. Differentiation 2002;70(9–10):537–46.

    Google Scholar 

  116. Tamariz E, Grinnell F. Modulation of fibroblast morphology and adhesion during collagen matrix remodeling. Mol Biol Cell 2002;13(11):3915–29.

    Google Scholar 

  117. Fringer J, Grinnell F. Fibroblast quiescence in floating collagen matrices: Decrease in serum activation of MEK and Raf but not Ras. J Biol Chem 2003;278(23):20612–7.

    Google Scholar 

  118. Fukamizu H, Grinnell F. Spatial organization of extracellular matrix and fibroblast activity: Effects of serum, transforming growth factor beta, and fibronectin. Exp Cell Res 1990;190(2):276–82.

    Google Scholar 

  119. Prajapati RT, Chavally-Mis B, Herbage D, Eastwood M, Brown RA. Mechanical loading regulates protease production by fibroblasts in three-dimensional collagen substrates. Wound Repair Regen 2000;8(3):226–37.

    Google Scholar 

  120. Fukuda S, Schmid-Schonbein GW. Regulation of CD18 expression on neutrophils in response to fluid shear stress. Proc Natl Acad Sci USA 2003;100(23):13152–7.

    Google Scholar 

  121. Shiu YT, Li S, Marganski WA, Usami S, Schwartz MA, Wang YL, et al. Rho mediates the shear-enhancement of endothelial cell migration and traction force generation. Biophys J 2004;86(4):2558–65.

    Google Scholar 

  122. Kleer CG, van Golen KL, Zhang Y, Wu ZF, Rubin MA, Merajver SD. Characterization of RhoC expression in benign and malignant breast disease: A potential new marker for small breast carcinomas with metastatic ability. Am J Pathol 2002;160(2):579–84.

    Google Scholar 

  123. van Golen KL, Bao L, DiVito MM, Wu Z, Prendergast GC, Merajver SD. Reversion of RhoC GTPase-induced inflammatory breast cancer phenotype by treatment with a farnesyl transferase inhibitor. Mol Cancer Ther 2002;1(8):575–83.

    Google Scholar 

  124. Day N, Warren R. Mammographic screening and mammographic patterns. Breast Cancer Res 2000;2(4):247–51.

    Google Scholar 

  125. Boyd NF, Jensen HM, Cooke G, Han HL. Relationship between mammographic and histological risk factors for breast cancer. J Natl Cancer Inst 1992;84(15):1170–9.

    Google Scholar 

  126. Alowami S, Troup S, Al-Haddad S, Kirkpatrick I, Watson PH. Mammographic density is related to stroma and stromal proteoglycan expression. Breast Cancer Res 2003;5(5):R129–35.

    Google Scholar 

  127. Beningo KA, Wang YL. Flexible substrata for the detection of cellular traction forces. Trends Cell Biol 2002;12(2):79–84.

    Google Scholar 

  128. Bershadsky AD, Balaban NQ, Geiger B. Adhesion-dependent cell mechanosensitivity. Annu Rev Cell Dev Biol 2003;19:677–95.

    Google Scholar 

  129. Harris AK, Wild P, Stopak D. Silicone rubber substrata: A new wrinkle in the study of cell locomotion. Science 1980;208:177–79.

    Google Scholar 

  130. Burton K, Taylor DL. Traction forces of cytokinesis measured with optically modified elastic substrata. Nature 1997;385(6615):450–4.

    Google Scholar 

  131. Burton K, Park JH, Taylor DL. Keratocytes generate traction forces in two phases. Mol Biol Cell 1999;10(11):3745–69.

    Google Scholar 

  132. Gaudet C, Marganski WA, Kim S, Brown CT, Gunderia V, Dembo M, et al. Influence of type I collagen surface density on fibroblast spreading, motility, and contractility. Biophys J 2003;85(5):3329–35.

    Google Scholar 

  133. Beningo KA, Lo CM, Wang YL. Flexible polyacrylamide substrata for the analysis of mechanical interactions at cell-substratum adhesions. Methods Cell Biol 2002;69:325–39.

    Google Scholar 

  134. Galbraith CG, Sheetz MP. A micromachined device provides a new bend on fibroblast traction forces. Proc Natl Acad Sci USA 1997;94(17):9114–8.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania

    Matthew J. Paszek

  2. Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania

    Valerie M. Weaver

  3. Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania

    Matthew J. Paszek & Valerie M. Weaver

  4. Department of Pathology, Institute for Medicine and Engineering, University of Pennsylvania, 1170 Vagelos Research Laboratory, 3340 Smith Walk, Philadelphia, Pennsylvania, 19104-6383

    Valerie M. Weaver

Authors
  1. Matthew J. Paszek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valerie M. Weaver
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Valerie M. Weaver.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paszek, M.J., Weaver, V.M. The Tension Mounts: Mechanics Meets Morphogenesis and Malignancy. J Mammary Gland Biol Neoplasia 9, 325–342 (2004). https://doi.org/10.1007/s10911-004-1404-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10911-004-1404-x

Keywords

Search

Navigation