Advertisement

Role of the Extracellular Matrix in Tumor Stroma: Barrier or Support?

  • Cédric Zeltz
  • Roya Navab
  • Marion Kusche-Gullberg
  • Ming-Sound Tsao
  • Donald Gullberg
Chapter

Abstract

Extensive evidence exists to functionally implicate stromal cancer-associated fibroblasts in tumor progression. Data from experimental cancer models has questioned the exclusive tumor-supportive function of the tumor stroma and suggested that the stroma might also act as a barrier to inhibit tumor metastasis. With consideration of this shift in dogma, we discuss the role of a specific part of the tumor stroma, the insoluble extracellular matrix (ECM), in tumor growth and spread. We summarize data from experimental tumor models on the role of fibrillar collagens, the fibronectin EDA splice form, proteoglycans, and the matricellular proteins, periostin and tenascins, which are all major components of the tumor stroma. In addition to the composition of the ECM being able to regulate tumorigenesis via integrin-mediated signaling, recent data indicate that the stiffness of the ECM also significantly impacts tumor growth and progression. These two properties add to the complexity of tumor-stroma interactions and have significant implications for gene regulation, matrix remodeling, and tumor metastasis. The role of the tumor stroma is thus extremely complex and highlights the importance of relating findings to tumor-type-, tissue-, and stage-specific effects in addition to considering inter-tumor and intra-tumor heterogeneity. Further work is needed to determine the relative contribution of different ECM proteins to the tumor-supporting and tumor-inhibiting roles of the tumor stroma.

Keywords

Tumor microenvironment Tumor stroma Extracellular matrix Fibrillar collagen Tumor growth Tumor metastasis Tumor stiffness Lysyl oxidase Fibronectin EDA Periostin Tenascins Proteoglycans 

Notes

Acknowledgments

We acknowledge the useful comments from Sandy Der (University Health Network, Toronto).

Supported by grants to DG from the Research Council of Norway (Norwegian Centres of Excellence grant, grants 2233250), the Western Norway Regional Health Authority (ID911899), and the Norwegian Cancer Society (id 3292722 to MKG).

References

  1. 1.
    Lu N, Karlsen TV, Reed RK, et al. Fibroblast alpha11beta1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids. PLoS One. 2014;9:e103173.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Osterholm C, Lu N, Liden A, et al. Fibroblast EXT1-levels influence tumor cell proliferation and migration in composite spheroids. PLoS One. 2012;7:e41334.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Ohlund D, Elyada E, Tuveson D. Fibroblast heterogeneity in the cancer wound. J Exp Med. 2014;211:1503–23.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Levental KR, Yu H, Kass L, et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell. 2009;139:891–906.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Weaver VM. The microenvironment matters. Mol Biol Cell. 2014;25:3254–8.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Zeltz C, Gullberg D. Post-translational modifications of integrin ligands as pathogenic mechanisms in disease. Matrix Biol. 2014;40:5–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Azmi AS, Bao B, Sarkar FH. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev. 2013;32:623–42.PubMedCrossRefGoogle Scholar
  8. 8.
    Hoshino A, Costa-Silva B, Shen TL, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527:329–35.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Cirri P, Chiarugi P. Cancer associated fibroblasts: the dark side of the coin. Am J Cancer Res. 2011;1:482–97.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Östman A, Augsten M. Cancer-associated fibroblasts and tumor growth – bystanders turning into key players. Curr Opin Genet Dev. 2009;19:67–73.PubMedCrossRefGoogle Scholar
  11. 11.
    Hu Y, Yan C, Mu L, et al. Fibroblast-derived exosomes contribute to chemoresistance through priming cancer stem cells in colorectal cancer. PLoS One. 2015;10:e0125625.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Eberlein C, Rooney C, Ross SJ, et al. E-Cadherin and EpCAM expression by NSCLC tumour cells associate with normal fibroblast activation through a pathway initiated by integrin alphavbeta6 and maintained through TGFbeta signalling. Oncogene. 2014;34:704–16.PubMedCrossRefGoogle Scholar
  13. 13.
    Eberlein C, Kendrew J, Mcdaid K, et al. A human monoclonal antibody 264RAD targeting alphavbeta6 integrin reduces tumour growth and metastasis, and modulates key biomarkers in vivo. Oncogene. 2013;32:4406–16.PubMedCrossRefGoogle Scholar
  14. 14.
    Henderson NC, Arnold TD, Katamura Y, et al. Targeting of alphav integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013;19:1617–24.PubMedCrossRefGoogle Scholar
  15. 15.
    Hinz B. The extracellular matrix and transforming growth factor-beta1: tale of a strained relationship. Matrix Biol. 2015;47:54–65.PubMedCrossRefGoogle Scholar
  16. 16.
    Klingberg F, Chow ML, Koehler A, et al. Prestress in the extracellular matrix sensitizes latent TGF-beta1 for activation. J Cell Biol. 2014;207:283–97.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Reed NI, Jo H, Chen C, et al. The alphavbeta1 integrin plays a critical in vivo role in tissue fibrosis. Sci Transl Med. 2015;7:288ra279.CrossRefGoogle Scholar
  18. 18.
    Gaggioli C, Hooper S, Hidalgo-Carcedo C, et al. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol. 2007;9:1392–400.PubMedCrossRefGoogle Scholar
  19. 19.
    Sanz-Moreno V, Gaggioli C, Yeo M, et al. ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma. Cancer Cell. 2011;20:229–45.PubMedCrossRefGoogle Scholar
  20. 20.
    Ozdemir BC, Pentcheva-Hoang T, Carstens JL, et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014;25:719–34.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Rhim AD, Oberstein PE, Thomas DH, et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014;25:735–47.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Driskell RR, Lichtenberger BM, Hoste E, et al. Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature. 2013;504:277–81.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Kramann R, Schneider RK, Dirocco DP, et al. Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell. 2015;16:51–66.PubMedCrossRefGoogle Scholar
  24. 24.
    Rinkevich Y, Walmsley GG, Hu MS, et al. Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential. Science. 2015;348:aaa2151.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Neesse A, Algul H, Tuveson DA, et al. Stromal biology and therapy in pancreatic cancer: a changing paradigm. Gut. 2015;64:1476–84.PubMedCrossRefGoogle Scholar
  26. 26.
    Ricard-Blum S. The collagen family. Cold Spring Harb Perspect Biol. 2011;3:a004978.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Rubashkin MG, Ou G, Weaver VM. Deconstructing signaling in three dimensions. Biochemistry. 2014;53:2078–90.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Egeblad M, Rasch MG, Weaver VM. Dynamic interplay between the collagen scaffold and tumor evolution. Curr Opin Cell Biol. 2010;22:697–706.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Dvorak HF. Tumors: wounds that do not heal-redux. Cancer Immunol Res. 2015;3:1–11.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Merkel JR, Dipaolo BR, Hallock GG, et al. Type I and type III collagen content of healing wounds in fetal and adult rats. Proc Soc Exp Biol Med. 1988;187:493–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Barczyk M, Carracedo S, Gullberg D. Integrins. Cell Tissue Res. 2010;339:269–80.PubMedCrossRefGoogle Scholar
  33. 33.
    Zeltz C, Gullberg D. The integrin-collagen connection – a glue for tissue repair? J Cell Sci. 2016;129:653–64.PubMedCrossRefGoogle Scholar
  34. 34.
    Zeltz C, Orgel J, Gullberg D. Molecular composition and function of integrin-based collagen glues-introducing COLINBRIs. Biochim Biophys Acta. 2014;1840:2533–48.PubMedCrossRefGoogle Scholar
  35. 35.
    Abbonante V, Gruppi C, Rubel D, et al. Discoidin domain receptor 1 protein is a novel modulator of megakaryocyte-collagen interactions. J Biol Chem. 2013;288:16738–46.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Staudinger LA, Spano SJ, Lee W, et al. Interactions between the discoidin domain receptor 1 and beta1 integrin regulate attachment to collagen. Biology Open. 2013;2:1148–59.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Xu H, Bihan D, Chang F, et al. Discoidin domain receptors promote alpha1beta1- and alpha2beta1-integrin mediated cell adhesion to collagen by enhancing integrin activation. PLoS One. 2012;7:e52209.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Cox TR, Erler JT. Molecular pathways: connecting fibrosis and solid tumor metastasis. Clin Cancer Res. 2014;20:3637–43.PubMedCrossRefGoogle Scholar
  39. 39.
    Dufort CC, Paszek MJ, Weaver VM. Balancing forces: architectural control of mechanotransduction. Nat Rev Mol Cell Biol. 2011;12:308–19.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Gilkes DM, Semenza GL, Wirtz D. Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat Rev Cancer. 2014;14:430–9.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Malik R, Lelkes PI, Cukierman E. Biomechanical and biochemical remodeling of stromal extracellular matrix in cancer. Trends Biotechnol. 2015;33:230–6.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Miller BW, Morton JP, Pinese M, et al. Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy. EMBO Mol Med. 2015;7:1063–76.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer. 2006;6:392–401.PubMedCrossRefGoogle Scholar
  44. 44.
    Cooke ME, Sakai T, Mosher DF. Contraction of collagen matrices mediated by a2b1A and avb3 integrins. J Cell Sci. 2000;113:2375–83.PubMedGoogle Scholar
  45. 45.
    Schulz JN, Zeltz C, Sorensen IW, et al. Reduced granulation tissue and wound strength in the absence of alpha11beta1 integrin. J Invest Dermatol. 2015;135:1435–44.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Gullberg D, Tingstrom A, Thuresson AC, et al. b1 integrin-mediated collagen gel contraction is stimulated by PDGF. Exp Cell Res. 1990;186:264–72.PubMedCrossRefGoogle Scholar
  47. 47.
    Jokinen J, Dadu E, Nykvist P, et al. Integrin-mediated cell adhesion to type I collagen fibrils. J Biol Chem. 2004;279:31956–63.PubMedCrossRefGoogle Scholar
  48. 48.
    Barczyk MM, Lu N, Popova SN, et al. Alpha11beta1 integrin-mediated MMP-13-dependent collagen lattice contraction by fibroblasts: evidence for integrin-coordinated collagen proteolysis. J Cell Physiol. 2013;228:1108–19.PubMedCrossRefGoogle Scholar
  49. 49.
    Ravanti L, Heino J, Lopez-Otin C, et al. Induction of collagenase-3 (MMP-13) expression in human skin fibroblasts by three-dimensional collagen is mediated by p38 mitogen-activated protein kinase. J Biol Chem. 1999;274:2446–55.PubMedCrossRefGoogle Scholar
  50. 50.
    Provenzano PP, Eliceiri KW, Keely PJ. Shining new light on 3D cell motility and the metastatic process. Trends Cell Biol. 2009;19:638–48.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Brisson BK, Mauldin EA, Lei W, et al. Type III collagen directs stromal organization and limits metastasis in a murine model of breast cancer. Am J Pathol. 2015;185:1471–86.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Nistico P, Bissell MJ, Radisky DC. Epithelial-mesenchymal transition: general principles and pathological relevance with special emphasis on the role of matrix metalloproteinases. Cold Spring Harb Perspect Biol. 2012;4:a011908.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Radisky D, Muschler J, Bissell MJ. Order and disorder: the role of extracellular matrix in epithelial cancer. Cancer Investig. 2002;20:139–53.CrossRefGoogle Scholar
  54. 54.
    Smith BN, Bhowmick NA. Role of EMT in metastasis and therapy resistance. J Clin Med. 2016;5:17.PubMedCentralCrossRefGoogle Scholar
  55. 55.
    Provenzano PP, Inman DR, Eliceiri KW, et al. Collagen density promotes mammary tumor initiation and progression. BMC Med. 2008;6:11.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Xiong G, Deng L, Zhu J, et al. Prolyl-4-hydroxylase alpha subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition. BMC Cancer. 2014;14:1.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Chen Y, Terajima M, Yang Y, et al. Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma. J Clin Invest. 2015;125:1147–62.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Montgomery AM, Reisfeld RA, Cheresh DA. Integrin alpha v beta 3 rescues melanoma cells from apoptosis in three-dimensional dermal collagen. Proc Natl Acad Sci U S A. 1994;91:8856–60.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Assent D, Bourgot I, Hennuy B, et al. A membrane-type-1 matrix metalloproteinase (MT1-MMP)-discoidin domain receptor 1 axis regulates collagen-induced apoptosis in breast cancer cells. PLoS One. 2015;10:e0116006.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Maquoi E, Assent D, Detilleux J, et al. MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis. Oncogene. 2011;31:480–93.PubMedCrossRefGoogle Scholar
  61. 61.
    Nielsen BS, Egeblad M, Rank F, et al. Matrix metalloproteinase 13 is induced in fibroblasts in polyomavirus middle T antigen-driven mammary carcinoma without influencing tumor progression. PLoS One. 2008;3:e2959.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Perry SW, Schueckler JM, Burke K, et al. Stromal matrix metalloprotease-13 knockout alters Collagen I structure at the tumor-host interface and increases lung metastasis of C57BL/6 syngeneic E0771 mammary tumor cells. BMC Cancer. 2013;13:411.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Krane SM, Byrne MH, Lemaitre V, et al. Different collagenase gene products have different roles in degradation of type I collagen. J Biol Chem. 1996;271:28509–15.PubMedCrossRefGoogle Scholar
  64. 64.
    Romanic AM, Adachi E, Kadler KE, et al. Copolymerization of pNcollagen III and collagen I. pNcollagen III decreases the rate of incorporation of collagen I into fibrils, the amount of collagen I incorporated, and the diameter of the fibrils formed. J Biol Chem. 1991;266:12703–9.PubMedGoogle Scholar
  65. 65.
    Lebert DC, Squirrell JM, Rindy J, et al. Matrix metalloproteinase 9 modulates collagen matrices and wound repair. Development. 2015;142:2136–46.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Herchenhan A, Uhlenbrock F, Eliasson P, et al. Lysyl oxidase activity is required for ordered collagen fibrillogenesis by tendon cells. J Biol Chem. 2015;290:16440–50.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Sabeh F, Shimizu-Hirota R, Weiss SJ. Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited. J Cell Biol. 2009;185:11–9.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Wolf K, Te Lindert M, Krause M, et al. Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force. J Cell Biol. 2013;201:1069–84.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Nishioka T, Eustace A, West C. Lysyl oxidase: from basic science to future cancer treatment. Cell Struct Funct. 2012;37:75–80.PubMedCrossRefGoogle Scholar
  70. 70.
    Cox TR, Erler JT. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis Model Mech. 2011;4:165–78.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Cox TR, Rumney RM, Schoof EM, et al. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature. 2015;522:106–10.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Kaplan RN, Riba RD, Zacharoulis S, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438:820–7.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Oskarsson T, Acharyya S, Zhang XH, et al. Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med. 2011;17:867–74.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Oskarsson T, Massague J. Extracellular matrix players in metastatic niches. EMBO J. 2012;31:254–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Wilgus ML, Borczuk AC, Stoopler M, et al. Lysyl oxidase: a lung adenocarcinoma biomarker of invasion and survival. Cancer. 2011;117:2186–91.PubMedCrossRefGoogle Scholar
  76. 76.
    Navab R, Strumpf D, To C, et al. Integrin alpha11beta1 regulates cancer stromal stiffness and promotes tumorigenicity and metastasis in non-small cell lung cancer. Oncogene. 2016;35:1899–908.PubMedCrossRefGoogle Scholar
  77. 77.
    Erler JT, Bennewith KL, Nicolau M, et al. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature. 2006;440:1222–6.PubMedCrossRefGoogle Scholar
  78. 78.
    Pupa SM, Menard S, Forti S, et al. New insights into the role of extracellular matrix during tumor onset and progression. J Cell Physiol. 2002;192:259–67.PubMedCrossRefGoogle Scholar
  79. 79.
    Theret N, Musso O, Turlin B, et al. Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas. Hepatology. 2001;34:82–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.PubMedCrossRefGoogle Scholar
  81. 81.
    Ronnov-Jessen L, Petersen OW, Bissell MJ. Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. Physiol Rev. 1996;76:69–125.PubMedCrossRefGoogle Scholar
  82. 82.
    Leitinger B, Hohenester E. Mammalian collagen receptors. Matrix Biol. 2007;26:146–55.PubMedCrossRefGoogle Scholar
  83. 83.
    Chen X, Nadiarynkh O, Plotnikov S, et al. Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure. Nat Protoc. 2012;7:654–69.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Tuer A, Tokarz D, Prent N, et al. Nonlinear multicontrast microscopy of hematoxylin-and-eosin-stained histological sections. J Biomed Opt. 2010;15:026018.PubMedCrossRefGoogle Scholar
  85. 85.
    Tuer AE, Akens MK, Krouglov S, et al. Hierarchical model of fibrillar collagen organization for interpreting the second-order susceptibility tensors in biological tissue. Biophys J. 2012;103:2093–105.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Tuer AE, Krouglov S, Prent N, et al. Nonlinear optical properties of type I collagen fibers studied by polarization dependent second harmonic generation microscopy. J Phys Chem B. 2011;115:12759–69.PubMedCrossRefGoogle Scholar
  87. 87.
    Amat-Roldan I, Psilodimitrakopoulos S, Loza-Alvarez P, et al. Fast image analysis in polarization SHG microscopy. Opt Express. 2010;18:17209–19.PubMedCrossRefGoogle Scholar
  88. 88.
    Golaraei A, Cisek R, Krouglov S, et al. Characterization of collagen in non-small cell lung carcinoma with second harmonic polarization microscopy. Biomed Opt Express. 2014;5:3562–7.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Strupler M, Pena AM, Hernest M, et al. Second harmonic imaging and scoring of collagen in fibrotic tissues. Opt Express. 2007;15:4054–65.PubMedCrossRefGoogle Scholar
  90. 90.
    Rezakhaniha R, Agianniotis A, Schrauwen JT, et al. Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy. Biomech Model Mechanobiol. 2012;11:461–73.PubMedCrossRefGoogle Scholar
  91. 91.
    Starborg T, Kalson NS, Lu Y, et al. Using transmission electron microscopy and 3View to determine collagen fibril size and three-dimensional organization. Nat Protoc. 2013;8:1433–48.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Paige MF, Rainey JK, Goh MC. A study of fibrous long spacing collagen ultrastructure and assembly by atomic force microscopy. Micron. 2001;32:341–53.PubMedCrossRefGoogle Scholar
  93. 93.
    Zhang J, Wang YL, Gu L, et al. Atomic force microscopy of actin. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2003;35:489–94.Google Scholar
  94. 94.
    Glatzel T, Holscher H, Schimmel T, et al. Advanced atomic force microscopy techniques. Beilstein J Nanotechnol. 2012;3:893–4.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Strasser S, Zink A, Janko M, et al. Structural investigations on native collagen type I fibrils using AFM. Biochem Biophys Res Commun. 2007;354:27–32.PubMedCrossRefGoogle Scholar
  96. 96.
    Lopez JI, Kang I, You WK, et al. In situ force mapping of mammary gland transformation. Integr Biol (Camb). 2011;3:910–21.CrossRefGoogle Scholar
  97. 97.
    Braet F, Vermijlen D, Bossuyt V, et al. Early detection of cytotoxic events between hepatic natural killer cells and colon carcinoma cells as probed with the atomic force microscope. Ultramicroscopy. 2001;89:265–73.PubMedCrossRefGoogle Scholar
  98. 98.
    Akhtar R, Schwarzer N, Sherratt MJ, et al. Nanoindentation of histological specimens: mapping the elastic properties of soft tissues. J Mater Res. 2009;24:638–46.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Gueta R, Barlam D, Shneck RZ, et al. Measurement of the mechanical properties of isolated tectorial membrane using atomic force microscopy. Proc Natl Acad Sci U S A. 2006;103:14790–5.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Barbone PE, Bamber JC. Quantitative elasticity imaging: what can and cannot be inferred from strain images. Phys Med Biol. 2002;47:2147–64.PubMedCrossRefGoogle Scholar
  101. 101.
    Jiang T, Olson ES, Nguyen QT, et al. Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proc Natl Acad Sci U S A. 2004;101:17867–72.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Scherer RL, Vansaun MN, Mcintyre JO, et al. Optical imaging of matrix metalloproteinase-7 activity in vivo using a proteolytic nanobeacon. Mol Imaging. 2008;7:118–31.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Littlepage LE, Sternlicht MD, Rougier N, et al. Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression. Cancer Res. 2010;70:2224–34.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Low AF, Tearney GJ, Bouma BE, et al. Technology Insight: optical coherence tomography – current status and future development. Nat Clin Pract Cardiovasc Med. 2006;3:154–62. quiz 172PubMedCrossRefGoogle Scholar
  105. 105.
    Miserus RJ, Herias MV, Prinzen L, et al. Molecular MRI of early thrombus formation using a bimodal alpha2-antiplasmin-based contrast agent. JACC Cardiovasc Imaging. 2009;2:987–96.PubMedCrossRefGoogle Scholar
  106. 106.
    Spuentrup E, Buecker A, Katoh M, et al. Molecular magnetic resonance imaging of coronary thrombosis and pulmonary emboli with a novel fibrin-targeted contrast agent. Circulation. 2005;111:1377–82.PubMedCrossRefGoogle Scholar
  107. 107.
    Stracke CP, Katoh M, Wiethoff AJ, et al. Molecular MRI of cerebral venous sinus thrombosis using a new fibrin-specific MR contrast agent. Stroke. 2007;38:1476–81.PubMedCrossRefGoogle Scholar
  108. 108.
    Hynes R. Molecular biology of fibronectin. Annu Rev Cell Biol. 1985;1:67–90.PubMedCrossRefGoogle Scholar
  109. 109.
    White ES, Baralle FE, Muro AF. New insights into form and function of fibronectin splice variants. J Pathol. 2008;216:1–14.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Astrof S, Crowley D, George EL, et al. Direct test of potential roles of EIIIA and EIIIB alternatively spliced segments of fibronectin in physiological and tumor angiogenesis. Mol Cell Biol. 2004;24:8662–70.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Singh P, Reimer CL, Peters JH, et al. The spatial and temporal expression patterns of integrin alpha9beta1 and one of its ligands, the EIIIA segment of fibronectin, in cutaneous wound healing. J Invest Dermatol. 2004;123:1176–81.PubMedCrossRefGoogle Scholar
  112. 112.
    Bhattacharyya S, Tamaki Z, Wang W, et al. FibronectinEDA promotes chronic cutaneous fibrosis through Toll-like receptor signaling. Sci Transl Med. 2014;6:232ra250.CrossRefGoogle Scholar
  113. 113.
    Rybinski B, Franco-Barraza J, Cukierman E. The wound healing, chronic fibrosis, and cancer progression triad. Physiol Genomics. 2014;46:223–44.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Rybak JN, Roesli C, Kaspar M, et al. The extra-domain A of fibronectin is a vascular marker of solid tumors and metastases. Cancer Res. 2007;67:10948–57.PubMedCrossRefGoogle Scholar
  115. 115.
    Matsumoto E, Yoshida T, Kawarada Y, et al. Expression of fibronectin isoforms in human breast tissue: production of extra domain A+/extra domain B+ by cancer cells and extra domain A+ by stromal cells. Jpn J Cancer Res. 1999;90:320–5.PubMedCrossRefGoogle Scholar
  116. 116.
    Pujuguet P, Hammann A, Moutet M, et al. Expression of fibronectin ED-A+ and ED-B+ isoforms by human and experimental colorectal cancer. Contribution of cancer cells and tumor-associated myofibroblasts. Am J Pathol. 1996;148:579–92.PubMedPubMedCentralGoogle Scholar
  117. 117.
    Manabe R, Ohe N, Maeda T, et al. Modulation of cell-adhesive activity of fibronectin by the alternatively spliced EDA segment. J Cell Biol. 1997;139:295–307.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Shinde AV, Bystroff C, Wang C, et al. Identification of the peptide sequences within the EIIIA (EDA) segment of fibronectin that mediate integrin alpha9beta1-dependent cellular activities. J Biol Chem. 2008;283:2858–70.PubMedCrossRefGoogle Scholar
  119. 119.
    Kohan M, Muro AF, White ES, et al. EDA-containing cellular fibronectin induces fibroblast differentiation through binding to alpha4beta7 integrin receptor and MAPK/Erk 1/2-dependent signaling. FASEB J. 2010;24:4503–12.PubMedCrossRefGoogle Scholar
  120. 120.
    Okamura Y, Watari M, Jerud ES, et al. The extra domain A of fibronectin activates Toll-like receptor 4. J Biol Chem. 2001;276:10229–33.PubMedCrossRefGoogle Scholar
  121. 121.
    Kelsh RM, Mckeown-Longo PJ, Clark RA. EDA fibronectin in keloids create a vicious cycle of fibrotic tumor formation. J Invest Dermatol. 2015;135:1714–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Bazigou E, Xie S, Chen C, et al. Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis. Dev Cell. 2009;17:175–86.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Fukuda T, Yoshida N, Kataoka Y, et al. Mice lacking the EDB segment of fibronectin develop normally but exhibit reduced cell growth and fibronectin matrix assembly in vitro. Cancer Res. 2002;62:5603–10.PubMedGoogle Scholar
  124. 124.
    Muro AF, Chauhan AK, Gajovic S, et al. Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan. J Cell Biol. 2003;162:149–60.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Astrof S, Crowley D, Hynes RO. Multiple cardiovascular defects caused by the absence of alternatively spliced segments of fibronectin. Dev Biol. 2007;311:11–24.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Danussi C, Del Bel Belluz L, Pivetta E, et al. EMILIN1/alpha9beta1 integrin interaction is crucial in lymphatic valve formation and maintenance. Mol Cell Biol. 2013;33:4381–94.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Serini G, Bochaton-Piallat ML, Ropraz P, et al. The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-beta1. J Cell Biol. 1998;142:873–81.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Shinde AV, Kelsh R, Peters JH, et al. The alpha4beta1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotype in dermal fibroblasts. Matrix Biol. 2015;41:26–35.PubMedCrossRefGoogle Scholar
  129. 129.
    Singh P, Chen C, Pal-Ghosh S, et al. Loss of integrin alpha9beta1 results in defects in proliferation, causing poor re-epithelialization during cutaneous wound healing. J Invest Dermatol. 2009;129:217–28.PubMedCrossRefGoogle Scholar
  130. 130.
    Nakayama Y, Kon S, Kurotaki D, et al. Blockade of interaction of alpha9 integrin with its ligands hinders the formation of granulation in cutaneous wound healing. Lab Investig. 2010;90:881–94.PubMedCrossRefGoogle Scholar
  131. 131.
    Muro AF, Moretti FA, Moore BB, et al. An essential role for fibronectin extra type III domain A in pulmonary fibrosis. Am J Respir Crit Care Med. 2008;177:638–45.PubMedCrossRefGoogle Scholar
  132. 132.
    Arslan F, Smeets MB, Riem Vis PW, et al. Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction. Circ Res. 2011;108:582–92.PubMedCrossRefGoogle Scholar
  133. 133.
    Ou J, Deng J, Wei X, et al. Fibronectin extra domain A (EDA) sustains CD133(+)/CD44(+) subpopulation of colorectal cancer cells. Stem Cell Res. 2013;11:820–33.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Xiang L, Xie G, Ou J, et al. The extra domain A of fibronectin increases VEGF-C expression in colorectal carcinoma involving the PI3K/AKT signaling pathway. PLoS One. 2012;7:e35378.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Ou J, Peng Y, Deng J, et al. Endothelial cell-derived fibronectin extra domain A promotes colorectal cancer metastasis via inducing epithelial-mesenchymal transition. Carcinogenesis. 2014;35:1661–70.PubMedCrossRefGoogle Scholar
  136. 136.
    Sun X, Fa P, Cui Z, et al. The EDA-containing cellular fibronectin induces epithelial-mesenchymal transition in lung cancer cells through integrin alpha9beta1-mediated activation of PI3-K/AKT and Erk1/2. Carcinogenesis. 2014;35:184–91.PubMedCrossRefGoogle Scholar
  137. 137.
    Ou J, Pan F, Geng P, et al. Silencing fibronectin extra domain A enhances radiosensitivity in nasopharyngeal carcinomas involving an FAK/Akt/JNK pathway. Int J Radiat Oncol Biol Phys. 2012;82:e685–91.PubMedCrossRefGoogle Scholar
  138. 138.
    Iozzo RV, Sanderson RD. Proteoglycans in cancer biology, tumour microenvironment and angiogenesis. J Cell Mol Med. 2011;15:1013–31.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Theocharis AD, Skandalis SS, Tzanakakis GN, et al. Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting. FEBS J. 2010;277:3904–23.PubMedCrossRefGoogle Scholar
  140. 140.
    Wegrowski Y, Maquart FX. Involvement of stromal proteoglycans in tumour progression. Crit Rev Oncol Hematol. 2004;49:259–68.PubMedCrossRefGoogle Scholar
  141. 141.
    Sarrazin S, Lamanna WC, Esko JD. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol. 2011;3:a004952.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Li J-P, Kusche-Gullberg M. Heparan sulfate: biosynthesis, structure and function. Int Rev Cell Mol Biol. 2016;325:215–73.PubMedCrossRefGoogle Scholar
  143. 143.
    Bishop JR, Schuksz M, Esko JD. Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature. 2007;446:1030–7.PubMedCrossRefGoogle Scholar
  144. 144.
    Ai X, Do AT, Lozynska O, et al. QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling. J Cell Biol. 2003;162:341–51.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Billings PC, Pacifici M. Interactions of signaling proteins, growth factors and other proteins with heparan sulfate: mechanisms and mysteries. Connect Tissue Res. 2015;56:272–80.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Dowsland MH, Harvey JR, Lennard TW, et al. Chemokines and breast cancer: a gateway to revolutionary targeted cancer treatments? Curr Med Chem. 2003;10:579–92.PubMedCrossRefGoogle Scholar
  147. 147.
    Lau EK, Paavola CD, Johnson Z, et al. Identification of the glycosaminoglycan binding site of the CC chemokine, MCP-1: implications for structure and function in vivo. J Biol Chem. 2004;279:22294–305.PubMedCrossRefGoogle Scholar
  148. 148.
    Iozzo RV, Schaefer L. Proteoglycan form and function: a comprehensive nomenclature of proteoglycans. Matrix Biol. 2015;42:11–55.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Choi Y, Chung H, Jung H, et al. Syndecans as cell surface receptors: unique structure equates with functional diversity. Matrix Biol. 2011;30:93–9.PubMedCrossRefGoogle Scholar
  150. 150.
    Couchman JR, Gopal S, Lim HC, et al. Syndecans: from peripheral coreceptors to mainstream regulators of cell behaviour. Int J Exp Pathol. 2015;96:1–10.PubMedCrossRefGoogle Scholar
  151. 151.
    Ihrcke NS, Platt JL. Shedding of heparan sulfate proteoglycan by stimulated endothelial cells: evidence for proteolysis of cell-surface molecules. J Cell Physiol. 1996;168:625–37.PubMedCrossRefGoogle Scholar
  152. 152.
    Choi S, Kim JY, Park JH, et al. The matrix metalloproteinase-7 regulates the extracellular shedding of syndecan-2 from colon cancer cells. Biochem Biophys Res Commun. 2012;417:1260–4.PubMedCrossRefGoogle Scholar
  153. 153.
    Manon-Jensen T, Itoh Y, Couchman JR. Proteoglycans in health and disease: the multiple roles of syndecan shedding. FEBS J. 2010;277:3876–89.PubMedCrossRefGoogle Scholar
  154. 154.
    Manon-Jensen T, Multhaupt HA, Couchman JR. Mapping of matrix metalloproteinase cleavage sites on syndecan-1 and syndecan-4 ectodomains. FEBS J. 2013;280:2320–31.PubMedCrossRefGoogle Scholar
  155. 155.
    Ding K, Lopez-Burks M, Sanchez-Duran JA, et al. Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. J Cell Biol. 2005;171:729–38.PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Tan X, Khalil N, Tesarik C, et al. Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases. Am J Physiol Lung Cell Mol Physiol. 2012;302:L700–10.PubMedCrossRefGoogle Scholar
  157. 157.
    Yang Y, Macleod V, Miao HQ, et al. Heparanase enhances syndecan-1 shedding: a novel mechanism for stimulation of tumor growth and metastasis. J Biol Chem. 2007;282:13326–33.PubMedCrossRefGoogle Scholar
  158. 158.
    Joensuu H, Anttonen A, Eriksson M, et al. Soluble syndecan-1 and serum basic fibroblast growth factor are new prognostic factors in lung cancer. Cancer Res. 2002;62:5210–7.PubMedGoogle Scholar
  159. 159.
    Seidel C, Sundan A, Hjorth M, et al. Serum syndecan-1: a new independent prognostic marker in multiple myeloma. Blood. 2000;95:388–92.PubMedGoogle Scholar
  160. 160.
    Szarvas T, Reis H, Kramer G, et al. Enhanced stromal syndecan-1 expression is an independent risk factor for poor survival in bladder cancer. Hum Pathol. 2014;45:674–82.PubMedCrossRefGoogle Scholar
  161. 161.
    Su G, Blaine SA, Qiao D, et al. Membrane type 1 matrix metalloproteinase-mediated stromal syndecan-1 shedding stimulates breast carcinoma cell proliferation. Cancer Res. 2008;68:9558–65.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Su G, Blaine SA, Qiao D, et al. Shedding of syndecan-1 by stromal fibroblasts stimulates human breast cancer cell proliferation via FGF2 activation. J Biol Chem. 2007;282:14906–15.PubMedCrossRefGoogle Scholar
  163. 163.
    Nikolova V, Koo CY, Ibrahim SA, et al. Differential roles for membrane-bound and soluble syndecan-1 (CD138) in breast cancer progression. Carcinogenesis. 2009;30:397–407.PubMedCrossRefGoogle Scholar
  164. 164.
    Choi S, Choi Y, Jun E, et al. Shed syndecan-2 enhances tumorigenic activities of colon cancer cells. Oncotarget. 2015;6:3874–86.PubMedPubMedCentralGoogle Scholar
  165. 165.
    Stewart MD, Ramani VC, Sanderson RD. Shed syndecan-1 translocates to the nucleus of cells delivering growth factors and inhibiting histone acetylation: a novel mechanism of tumor-host cross-talk. J Biol Chem. 2015;290:941–9.PubMedCrossRefGoogle Scholar
  166. 166.
    Ramani VC, Sanderson RD. Chemotherapy stimulates syndecan-1 shedding: a potentially negative effect of treatment that may promote tumor relapse. Matrix Biol. 2014;35:215–22.PubMedCrossRefGoogle Scholar
  167. 167.
    Wang X, Zuo D, Chen Y, et al. Shed Syndecan-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer. Br J Cancer. 2014;111:1965–76.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Chen S, Birk DE. The regulatory roles of small leucine-rich proteoglycans in extracellular matrix assembly. FEBS J. 2013;280:2120–37.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Cawthorn TR, Moreno JC, Dharsee M, et al. Proteomic analyses reveal high expression of decorin and endoplasmin (HSP90B1) are associated with breast cancer metastasis and decreased survival. PLoS One. 2012;7:e30992.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Sainio A, Nyman M, Lund R, et al. Lack of decorin expression by human bladder cancer cells offers new tools in the therapy of urothelial malignancies. PLoS One. 2013;8:e76190.PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Henke A, Grace OC, Ashley GR, et al. Stromal expression of decorin, Semaphorin6D, SPARC, Sprouty1 and Tsukushi in developing prostate and decreased levels of decorin in prostate cancer. PLoS One. 2012;7:e42516.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Campioni M, Ambrogi V, Pompeo E, et al. Identification of genes down-regulated during lung cancer progression: a cDNA array study. J Exp Clin Cancer Res. 2008;27:38.PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Bostrom P, Sainio A, Kakko T, et al. Localization of decorin gene expression in normal human breast tissue and in benign and malignant tumors of the human breast. Histochem Cell Biol. 2013;139:161–71.PubMedCrossRefGoogle Scholar
  174. 174.
    Oda G, Sato T, Ishikawa T, et al. Significance of stromal decorin expression during the progression of breast cancer. Oncol Rep. 2012;28:2003–8.PubMedCrossRefGoogle Scholar
  175. 175.
    Troup S, Njue C, Kliewer EV, et al. Reduced expression of the small leucine-rich proteoglycans, lumican, and decorin is associated with poor outcome in node-negative invasive breast cancer. Clin Cancer Res. 2003;9:207–14.PubMedGoogle Scholar
  176. 176.
    Horvath Z, Kovalszky I, Fullar A, et al. Decorin deficiency promotes hepatic carcinogenesis. Matrix Biol. 2014;35:194–205.PubMedCrossRefGoogle Scholar
  177. 177.
    Xu W, Neill T, Yang Y, et al. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer. Gene Ther. 2015;22:31–40.CrossRefGoogle Scholar
  178. 178.
    Bi X, Pohl NM, Qian Z, et al. Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice. Carcinogenesis. 2012;33:326–30.PubMedCrossRefGoogle Scholar
  179. 179.
    Nyman MC, Sainio AO, Pennanen MM, et al. Decorin in human colon cancer: localization in vivo and effect on cancer cell behavior in vitro. J Histochem Cytochem. 2015;63:710–20.PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Buraschi S, Neill T, Owens RT, et al. Decorin protein core affects the global gene expression profile of the tumor microenvironment in a triple-negative orthotopic breast carcinoma xenograft model. PLoS One. 2012;7:e45559.PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Goldoni S, Iozzo RV. Tumor microenvironment: modulation by decorin and related molecules harboring leucine-rich tandem motifs. Int J Cancer. 2008;123:2473–9.PubMedCrossRefGoogle Scholar
  182. 182.
    Buraschi S, Pal N, Tyler-Rubinstein N, et al. Decorin antagonizes Met receptor activity and down-regulates {beta}-catenin and Myc levels. J Biol Chem. 2010;285:42075–85.PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Neill T, Torres A, Buraschi S, et al. Decorin induces mitophagy in breast carcinoma cells via peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and mitostatin. J Biol Chem. 2014;289:4952–68.PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Buraschi S, Neill T, Goyal A, et al. Decorin causes autophagy in endothelial cells via Peg3. Proc Natl Acad Sci U S A. 2013;110:E2582–91.PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Neill T, Painter H, Buraschi S, et al. Decorin antagonizes the angiogenic network: concurrent inhibition of Met, hypoxia inducible factor 1alpha, vascular endothelial growth factor A, and induction of thrombospondin-1 and TIMP3. J Biol Chem. 2012;287:5492–506.PubMedCrossRefGoogle Scholar
  186. 186.
    Morcavallo A, Buraschi S, Xu SQ, et al. Decorin differentially modulates the activity of insulin receptor isoform A ligands. Matrix Biol. 2014;35:82–90.PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Kasamatsu A, Uzawa K, Minakawa Y, et al. Decorin in human oral cancer: a promising predictive biomarker of S-1 neoadjuvant chemosensitivity. Biochem Biophys Res Commun. 2015;457:71–6.PubMedCrossRefGoogle Scholar
  188. 188.
    Koninger J, Giese NA, Di Mola FF, et al. Overexpressed decorin in pancreatic cancer: potential tumor growth inhibition and attenuation of chemotherapeutic action. Clin Cancer Res. 2004;10:4776–83.PubMedCrossRefGoogle Scholar
  189. 189.
    Aprile G, Avellini C, Reni M, et al. Biglycan expression and clinical outcome in patients with pancreatic adenocarcinoma. Tumour Biol. 2013;34:131–7.PubMedCrossRefGoogle Scholar
  190. 190.
    Zhu YH, Yang F, Zhang SS, et al. High expression of biglycan is associated with poor prognosis in patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2013;6:2497–505.PubMedPubMedCentralGoogle Scholar
  191. 191.
    Hu L, Duan YT, Li JF, et al. Biglycan enhances gastric cancer invasion by activating FAK signaling pathway. Oncotarget. 2014;5:1885–96.PubMedPubMedCentralGoogle Scholar
  192. 192.
    Niedworok C, Rock K, Kretschmer I, et al. Inhibitory role of the small leucine-rich proteoglycan biglycan in bladder cancer. PLoS One. 2013;8:e80084.PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Weber CK, Sommer G, Michl P, et al. Biglycan is overexpressed in pancreatic cancer and induces G1-arrest in pancreatic cancer cell lines. Gastroenterology. 2001;121:657–67.PubMedCrossRefGoogle Scholar
  194. 194.
    Corpuz LM, Funderburgh JL, Funderburgh ML, et al. Molecular cloning and tissue distribution of keratocan. Bovine corneal keratan sulfate proteoglycan 37A. J Biol Chem. 1996;271:9759–63.PubMedCrossRefGoogle Scholar
  195. 195.
    Brezillon S, Pietraszek K, Maquart FX, et al. Lumican effects in the control of tumour progression and their links with metalloproteinases and integrins. FEBS J. 2013;280:2369–81.PubMedCrossRefGoogle Scholar
  196. 196.
    Nikitovic D, Papoutsidakis A, Karamanos NK, et al. Lumican affects tumor cell functions, tumor-ECM interactions, angiogenesis and inflammatory response. Matrix Biol. 2014;35:206–14.PubMedCrossRefGoogle Scholar
  197. 197.
    Seya T, Tanaka N, Shinji S, et al. Lumican expression in advanced colorectal cancer with nodal metastasis correlates with poor prognosis. Oncol Rep. 2006;16:1225–30.PubMedGoogle Scholar
  198. 198.
    De Wit M, Belt EJ, Delis-Van Diemen PM, et al. Lumican and versican are associated with good outcome in stage II and III colon cancer. Ann Surg Oncol. 2013;20(Suppl 3):S348–59.PubMedCrossRefGoogle Scholar
  199. 199.
    Panis C, Pizzatti L, Herrera AC, et al. Putative circulating markers of the early and advanced stages of breast cancer identified by high-resolution label-free proteomics. Cancer Lett. 2013;330:57–66.PubMedCrossRefGoogle Scholar
  200. 200.
    Ishiwata T, Cho K, Kawahara K, et al. Role of lumican in cancer cells and adjacent stromal tissues in human pancreatic cancer. Oncol Rep. 2007;18:537–43.PubMedGoogle Scholar
  201. 201.
    Li X, Truty MA, Kang Y, et al. Extracellular lumican inhibits pancreatic cancer cell growth and is associated with prolonged survival after surgery. Clin Cancer Res. 2014;20:6529–40.PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    Matsuda Y, Yamamoto T, Kudo M, et al. Expression and roles of lumican in lung adenocarcinoma and squamous cell carcinoma. Int J Oncol. 2008;33:1177–85.PubMedGoogle Scholar
  203. 203.
    Brezillon S, Venteo L, Ramont L, et al. Expression of lumican, a small leucine-rich proteoglycan with antitumour activity, in human malignant melanoma. Clin Exp Dermatol. 2007;32:405–16.PubMedCrossRefGoogle Scholar
  204. 204.
    Brezillon S, Radwanska A, Zeltz C, et al. Lumican core protein inhibits melanoma cell migration via alterations of focal adhesion complexes. Cancer Lett. 2009;283:92–100.PubMedCrossRefGoogle Scholar
  205. 205.
    Zeltz C, Brezillon S, Kapyla J, et al. Lumican inhibits cell migration through alpha2beta1 integrin. Exp Cell Res. 2010;316:2922–31.PubMedCrossRefGoogle Scholar
  206. 206.
    Zeltz C, Brezillon S, Perreau C, et al. Lumcorin: a leucine-rich repeat 9-derived peptide from human lumican inhibiting melanoma cell migration. FEBS Lett. 2009;583:3027–32.PubMedCrossRefGoogle Scholar
  207. 207.
    Pietraszek K, Chatron-Colliet A, Brezillon S, et al. Lumican: a new inhibitor of matrix metalloproteinase-14 activity. FEBS Lett. 2014;588:4319–24.PubMedCrossRefGoogle Scholar
  208. 208.
    Coulson-Thomas VJ, Coulson-Thomas YM, Gesteira TF, et al. Lumican expression, localization and antitumor activity in prostate cancer. Exp Cell Res. 2013;319:967–81.PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Radwanska A, Litwin M, Nowak D, et al. Overexpression of lumican affects the migration of human colon cancer cells through up-regulation of gelsolin and filamentous actin reorganization. Exp Cell Res. 2012;318:2312–23.PubMedCrossRefGoogle Scholar
  210. 210.
    Oldberg A, Kalamajski S, Salnikov AV, et al. Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinoma. Proc Natl Acad Sci U S A. 2007;104:13966–71.PubMedPubMedCentralCrossRefGoogle Scholar
  211. 211.
    Hildebrand A, Romaris M, Rasmussen LM, et al. Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta. Biochem J. 1994;302(Pt 2):527–34.PubMedPubMedCentralCrossRefGoogle Scholar
  212. 212.
    Maris P, Blomme A, Palacios AP, et al. Asporin is a fibroblast-derived TGF-beta1 inhibitor and a tumor suppressor associated with good prognosis in breast cancer. PLoS Med. 2015;12:e1001871.PubMedPubMedCentralCrossRefGoogle Scholar
  213. 213.
    Mosher DF, Adams JC. Adhesion-modulating/matricellular ECM protein families: a structural, functional and evolutionary appraisal. Matrix Biol. 2012;31:155–61.PubMedCrossRefGoogle Scholar
  214. 214.
    Wong GS, Rustgi AK. Matricellular proteins: priming the tumour microenvironment for cancer development and metastasis. Br J Cancer. 2013;108:755–61.PubMedPubMedCentralCrossRefGoogle Scholar
  215. 215.
    Chiquet-Ehrismann R, Tucker RP. Tenascins and the importance of adhesion modulation. Cold Spring Harb Perspect Biol. 2011;3:a004960.PubMedPubMedCentralCrossRefGoogle Scholar
  216. 216.
    Orend G, Chiquet-Ehrismann R. Tenascin-C induced signaling in cancer. Cancer Lett. 2006;244:143–63.PubMedCrossRefGoogle Scholar
  217. 217.
    Martin D, Brown-Luedi M, Chiquet-Ehrismann R. Tenascin-C signaling through induction of 14-3-3 tau. J Cell Biol. 2003;160:171–5.PubMedPubMedCentralCrossRefGoogle Scholar
  218. 218.
    Ruiz C, Huang W, Hegi ME, et al. Growth promoting signaling by tenascin-C [corrected]. Cancer Res. 2004;64:7377–85.PubMedCrossRefGoogle Scholar
  219. 219.
    Huang W, Chiquet-Ehrismann R, Moyano JV, et al. Interference of tenascin-C with syndecan-4 binding to fibronectin blocks cell adhesion and stimulates tumor cell proliferation. Cancer Res. 2001;61:8586–94.PubMedGoogle Scholar
  220. 220.
    Shi M, He X, Wei W, et al. Tenascin-C induces resistance to apoptosis in pancreatic cancer cell through activation of ERK/NF-kappaB pathway. Apoptosis. 2015;20:843–57.PubMedCrossRefGoogle Scholar
  221. 221.
    Katoh D, Nagaharu K, Shimojo N, et al. Binding of alphavbeta1 and alphavbeta6 integrins to tenascin-C induces epithelial-mesenchymal transition-like change of breast cancer cells. Oncogene. 2013;2:e65.CrossRefGoogle Scholar
  222. 222.
    Nagaharu K, Zhang X, Yoshida T, et al. Tenascin C induces epithelial-mesenchymal transition-like change accompanied by SRC activation and focal adhesion kinase phosphorylation in human breast cancer cells. Am J Pathol. 2011;178:754–63.PubMedPubMedCentralCrossRefGoogle Scholar
  223. 223.
    Ghahhari NM, Babashah S. Interplay between microRNAs and WNT/beta-catenin signalling pathway regulates epithelial-mesenchymal transition in cancer. Eur J Cancer. 2015;51:1638–49.PubMedCrossRefGoogle Scholar
  224. 224.
    Saupe F, Schwenzer A, Jia Y, et al. Tenascin-C downregulates wnt inhibitor dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model. Cell Rep. 2013;5:482–92.PubMedCrossRefGoogle Scholar
  225. 225.
    Beiter K, Hiendlmeyer E, Brabletz T, et al. Beta-Catenin regulates the expression of tenascin-C in human colorectal tumors. Oncogene. 2005;24:8200–4.PubMedCrossRefGoogle Scholar
  226. 226.
    Grahovac J, Becker D, Wells A. Melanoma cell invasiveness is promoted at least in part by the epidermal growth factor-like repeats of tenascin-C. J Invest Dermatol. 2013;133:210–20.PubMedCrossRefGoogle Scholar
  227. 227.
    Nong Y, Wu D, Lin Y, et al. Tenascin-C expression is associated with poor prognosis in hepatocellular carcinoma (HCC) patients and the inflammatory cytokine TNF-alpha-induced TNC expression promotes migration in HCC cells. Am J Cancer Res. 2015;5:782–91.PubMedPubMedCentralGoogle Scholar
  228. 228.
    Kaariainen E, Nummela P, Soikkeli J, et al. Switch to an invasive growth phase in melanoma is associated with tenascin-C, fibronectin, and procollagen-I forming specific channel structures for invasion. J Pathol. 2006;210:181–91.PubMedCrossRefGoogle Scholar
  229. 229.
    Hancox RA, Allen MD, Holliday DL, et al. Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms. Breast Cancer Res. 2009;11:R24.PubMedPubMedCentralCrossRefGoogle Scholar
  230. 230.
    Kalembeyi I, Inada H, Nishiura R, et al. Tenascin-C upregulates matrix metalloproteinase-9 in breast cancer cells: direct and synergistic effects with transforming growth factor beta1. Int J Cancer. 2003;105:53–60.PubMedCrossRefGoogle Scholar
  231. 231.
    Calvo A, Catena R, Noble MS, et al. Identification of VEGF-regulated genes associated with increased lung metastatic potential: functional involvement of tenascin-C in tumor growth and lung metastasis. Oncogene. 2008;27:5373–84.PubMedPubMedCentralCrossRefGoogle Scholar
  232. 232.
    O’connell JT, Sugimoto H, Cooke VG, et al. VEGF-A and Tenascin-C produced by S100A4+ stromal cells are important for metastatic colonization. Proc Natl Acad Sci U S A. 2011;108:16002–7.PubMedPubMedCentralCrossRefGoogle Scholar
  233. 233.
    Chiovaro F, Martina E, Bottos A, et al. Transcriptional regulation of tenascin-W by TGF-beta signaling in the bone metastatic niche of breast cancer cells. Int J Cancer. 2015;137:1842–54.PubMedPubMedCentralCrossRefGoogle Scholar
  234. 234.
    Degen M, Brellier F, Kain R, et al. Tenascin-W is a novel marker for activated tumor stroma in low-grade human breast cancer and influences cell behavior. Cancer Res. 2007;67:9169–79.PubMedCrossRefGoogle Scholar
  235. 235.
    Degen M, Brellier F, Schenk S, et al. Tenascin-W, a new marker of cancer stroma, is elevated in sera of colon and breast cancer patients. Int J Cancer. 2008;122:2454–61.PubMedCrossRefGoogle Scholar
  236. 236.
    Scherberich A, Tucker RP, Degen M, et al. Tenascin-W is found in malignant mammary tumors, promotes alpha8 integrin-dependent motility and requires p38MAPK activity for BMP-2 and TNF-alpha induced expression in vitro. Oncogene. 2005;24:1525–32.PubMedCrossRefGoogle Scholar
  237. 237.
    Brellier F, Martina E, Degen M, et al. Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors. BMC Clin Pathol. 2012;12:14.PubMedPubMedCentralCrossRefGoogle Scholar
  238. 238.
    Matsumoto K, Saga Y, Ikemura T, et al. The distribution of tenascin-X is distinct and often reciprocal to that of tenascin-C. J Cell Biol. 1994;125:483–93.PubMedCrossRefGoogle Scholar
  239. 239.
    Chiquet-Ehrismann R, Chiquet M. Tenascins: regulation and putative functions during pathological stress. J Pathol. 2003;200:488–99.PubMedCrossRefGoogle Scholar
  240. 240.
    Geffrotin C, Horak V, Crechet F, et al. Opposite regulation of tenascin-C and tenascin-X in MeLiM swine heritable cutaneous malignant melanoma. Biochim Biophys Acta. 2000;1524:196–202.PubMedCrossRefGoogle Scholar
  241. 241.
    Matsumoto K, Takayama N, Ohnishi J, et al. Tumour invasion and metastasis are promoted in mice deficient in tenascin-X. Genes Cells. 2001;6:1101–11.PubMedCrossRefGoogle Scholar
  242. 242.
    Matsumoto K, Minamitani T, Orba Y, et al. Induction of matrix metalloproteinase-2 by tenascin-X deficiency is mediated through the c-Jun N-terminal kinase and protein tyrosine kinase phosphorylation pathway. Exp Cell Res. 2004;297:404–14.PubMedCrossRefGoogle Scholar
  243. 243.
    Alcaraz LB, Exposito JY, Chuvin N, et al. Tenascin-X promotes epithelial-to-mesenchymal transition by activating latent TGF-beta. J Cell Biol. 2014;205:409–28.PubMedPubMedCentralCrossRefGoogle Scholar
  244. 244.
    Rios H, Koushik SV, Wang H, et al. periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype. Mol Cell Biol. 2005;25:11131–44.PubMedPubMedCentralCrossRefGoogle Scholar
  245. 245.
    Elliott CG, Wang J, Guo X, et al. Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair. J Cell Sci. 2012;125:121–32.PubMedPubMedCentralCrossRefGoogle Scholar
  246. 246.
    Lorts A, Schwanekamp JA, Baudino TA, et al. Deletion of periostin reduces muscular dystrophy and fibrosis in mice by modulating the transforming growth factor-beta pathway. Proc Natl Acad Sci U S A. 2012;109:10978–83.PubMedPubMedCentralCrossRefGoogle Scholar
  247. 247.
    Shimazaki M, Nakamura K, Kii I, et al. Periostin is essential for cardiac healing after acute myocardial infarction. J Exp Med. 2008;205:295–303.PubMedPubMedCentralCrossRefGoogle Scholar
  248. 248.
    Egbert M, Ruetze M, Sattler M, et al. The matricellular protein periostin contributes to proper collagen function and is downregulated during skin aging. J Dermatol Sci. 2013;73:40–8.PubMedCrossRefGoogle Scholar
  249. 249.
    Norris RA, Damon B, Mironov V, et al. Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues. J Cell Biochem. 2007;101:695–711.PubMedPubMedCentralCrossRefGoogle Scholar
  250. 250.
    Shimazaki M, Kudo A. Impaired capsule formation of tumors in periostin-null mice. Biochem Biophys Res Commun. 2008;367:736–42.PubMedCrossRefGoogle Scholar
  251. 251.
    Fukuda K, Sugihara E, Ohta S, et al. Periostin is a key niche component for wound metastasis of melanoma. PLoS One. 2015;10:e0129704.PubMedPubMedCentralCrossRefGoogle Scholar
  252. 252.
    Kikuchi Y, Kunita A, Iwata C, et al. The niche component periostin is produced by cancer-associated fibroblasts, supporting growth of gastric cancer through ERK activation. Am J Pathol. 2014;184:859–70.PubMedCrossRefGoogle Scholar
  253. 253.
    Zhou W, Ke SQ, Huang Z, et al. Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth. Nat Cell Biol. 2015;17:170–82.PubMedPubMedCentralCrossRefGoogle Scholar
  254. 254.
    Malanchi I, Santamaria-Martinez A, Susanto E, et al. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature. 2012;481:85–9.CrossRefGoogle Scholar
  255. 255.
    Andrikopoulos K, Liu X, Keene DR, et al. Targeted mutation in the col5a2 gene reveals a regulatory role for type V collagen during matrix assembly. Nat Genet. 1995;9:31–6.PubMedCrossRefGoogle Scholar
  256. 256.
    Lohler J, Timpl R, Jaenisch R. Embryonic lethal mutation in mouse collagen I gene causes rupture of blood vessels and is associated with erythropoietic and mesenchymal cell death. Cell. 1984;38:597–607.PubMedCrossRefGoogle Scholar
  257. 257.
    Wenstrup RJ, Florer JB, Brunskill EW, et al. Type V collagen controls the initiation of collagen fibril assembly. J Biol Chem. 2004;279:53331–7.PubMedCrossRefGoogle Scholar
  258. 258.
    Liu X, Wu H, Byrne M, et al. Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development. Proc Natl Acad Sci U S A. 1997;94:1852–6.PubMedPubMedCentralCrossRefGoogle Scholar
  259. 259.
    Liu X, Wu H, Byrne M, et al. A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling. J Cell Biol. 1995;130:227–37.PubMedCrossRefGoogle Scholar
  260. 260.
    Kii I, Amizuka N, Minqi L, et al. Periostin is an extracellular matrix protein required for eruption of incisors in mice. Biochem Biophys Res Commun. 2006;342:766–72.PubMedCrossRefGoogle Scholar
  261. 261.
    Ishiba T, Nagahara M, Nakagawa T, et al. Periostin suppression induces decorin secretion leading to reduced breast cancer cell motility and invasion. Sci Rep. 2014;4:7069.PubMedPubMedCentralCrossRefGoogle Scholar
  262. 262.
    Ontsuka K, Kotobuki Y, Shiraishi H, et al. Periostin, a matricellular protein, accelerates cutaneous wound repair by activating dermal fibroblasts. Exp Dermatol. 2012;21:331–6.PubMedCrossRefGoogle Scholar
  263. 263.
    Danielson KG, Baribault H, Holmes DF, et al. Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol. 1997;136:729–43.PubMedPubMedCentralCrossRefGoogle Scholar
  264. 264.
    Chakravarti S, Magnuson T, Lass JH, et al. Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J Cell Biol. 1998;141:1277–86.PubMedPubMedCentralCrossRefGoogle Scholar
  265. 265.
    Stepp MA, Daley WP, Bernstein AM, et al. Syndecan-1 regulates cell migration and fibronectin fibril assembly. Exp Cell Res. 2010;316:2322–39.PubMedPubMedCentralCrossRefGoogle Scholar
  266. 266.
    Goldoni S, Seidler DG, Heath J, et al. An antimetastatic role for decorin in breast cancer. Am J Pathol. 2008;173:844–55.PubMedPubMedCentralCrossRefGoogle Scholar
  267. 267.
    Beauvais DM, Burbach BJ, Rapraeger AC. The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells. J Cell Biol. 2004;167:171–81.PubMedPubMedCentralCrossRefGoogle Scholar
  268. 268.
    Mcquade KJ, Beauvais DM, Burbach BJ, et al. Syndecan-1 regulates alphavbeta5 integrin activity in B82L fibroblasts. J Cell Sci. 2006;119:2445–56.PubMedCrossRefGoogle Scholar
  269. 269.
    Vuoriluoto K, Jokinen J, Kallio K, et al. Syndecan-1 supports integrin alpha2beta1-mediated adhesion to collagen. Exp Cell Res. 2008;314:3369–81.PubMedCrossRefGoogle Scholar
  270. 270.
    Beauvais DM, Ell BJ, Mcwhorter AR, et al. Syndecan-1 regulates {alpha}v{beta}3 and {alpha}v{beta}5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor. J Exp Med. 2009;16:691–705.CrossRefGoogle Scholar
  271. 271.
    Vuillermoz B, Khoruzhenko A, D’onofrio MF, et al. The small leucine-rich proteoglycan lumican inhibits melanoma progression. Exp Cell Res. 2004;296:294–306.PubMedCrossRefGoogle Scholar
  272. 272.
    Yang Y, Macleod V, Dai Y, et al. The syndecan-1 heparan sulfate proteoglycan is a viable target for myeloma therapy. Blood. 2007;110:2041–8.PubMedPubMedCentralCrossRefGoogle Scholar
  273. 273.
    Hendaoui I, Tucker RP, Zingg D, et al. Tenascin-C is required for normal Wnt/beta-catenin signaling in the whisker follicle stem cell niche. Matrix Biol. 2014;40:46–53.PubMedCrossRefGoogle Scholar
  274. 274.
    Saga Y, Yagi T, Ikawa Y, et al. Mice develop normally without tenascin. Genes Dev. 1992;6:1821–31.PubMedCrossRefGoogle Scholar
  275. 275.
    Mao JR, Taylor G, Dean WB, et al. Tenascin-X deficiency mimics Ehlers-Danlos syndrome in mice through alteration of collagen deposition. Nat Genet. 2002;30:421–5.PubMedCrossRefGoogle Scholar
  276. 276.
    Tucker RP, Chiquet-Ehrismann R. Tenascin-C: its functions as an integrin ligand. Int J Biochem Cell Biol. 2015;65:165–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Cédric Zeltz
    • 1
  • Roya Navab
    • 2
  • Marion Kusche-Gullberg
    • 3
  • Ming-Sound Tsao
    • 4
  • Donald Gullberg
    • 3
  1. 1.Princess Margaret Cancer CentreUniversity Health NetworkTorontoCanada
  2. 2.Princess Margaret Cancer CentreUniversity Health NetworkTorontoCanada
  3. 3.Department of BiomedicineUniversity of BergenBergenNorway
  4. 4.Princess Margaret Cancer Centre, University Health Network, Departments of Laboratory MedicinePathobiology and Medical Biophysics, University of Toronto, Princess Margaret Cancer Research TowerTorontoCanada

Personalised recommendations