Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer

DMM Disease Models and Mechanisms - Tập 4 Số 2 - Trang 165-178 - 2011
Thomas R. Cox1, Janine T. Erler1
1Cancer Research UK Tumour Cell Signalling Unit, Section of Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK

Tóm tắt

Dynamic remodeling of the extracellular matrix (ECM) is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.

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Tài liệu tham khảo

Abraham, 2005, Scleroderma: from cell and molecular mechanisms to disease models, Trends Immunol., 26, 587, 10.1016/j.it.2005.09.004

Aggarwal, 2009, Inflammation and cancer: how friendly is the relationship for cancer patients?, Curr. Opin. Pharmacol., 9, 351, 10.1016/j.coph.2009.06.020

Ahn, 2008, Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells, Cancer Cell, 13, 193, 10.1016/j.ccr.2007.11.032

Akhtar, 2009, Mapping the micromechanical properties of cryo-sectioned aortic tissue with scanning acoustic microscopy, Mater. Res. Soc. Symp. Proc., 1132E

Akhtar, 2009, Nanoindentation of histological specimens: mapping the elastic properties of soft tissues, J. Mater. Res., 24, 638, 10.1557/jmr.2009.0130

Alcaraz, 2008, Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia, EMBO J., 27, 2829, 10.1038/emboj.2008.206

Arnold, 2010, Lack of host SPARC enhances vascular function and tumor spread in an orthotopic murine model of pancreatic carcinoma, Dis. Model. Mech., 3, 57, 10.1242/dmm.003228

Avery, 2006, The effects of the Maillard reaction on the physical properties and cell interactions of collagen, Pathol. Biol. (Paris), 54, 387, 10.1016/j.patbio.2006.07.005

Baker, 2010, The biomechanical integrin, J. Biomech., 43, 38, 10.1016/j.jbiomech.2009.09.007

Barbone, 2002, Quantitative elasticity imaging: what can and cannot be inferred from strain images, Phys. Med. Biol., 47, 2147, 10.1088/0031-9155/47/12/310

Barcellos-Hoff, 1989, Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane, Development, 105, 223, 10.1242/dev.105.2.223

Barry-Hamilton, 2010, Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment, Nat. Med., 16, 1009, 10.1038/nm.2208

Beloussov, 2000, Tension-dependent collective cell movements in the early gastrula ectoderm of Xenopus laevis embryos, Dev. Genes. Evol., 210, 92, 10.1007/s004270050015

Ben-Baruch, 2006, The multifaceted roles of chemokines in malignancy, Cancer Metastasis Rev., 25, 357, 10.1007/s10555-006-9003-5

Bennewith, 2009, The role of tumor cell-derived connective tissue growth factor (CTGF/CCN2) in pancreatic tumor growth, Cancer Res., 69, 775, 10.1158/0008-5472.CAN-08-0987

Berkenblit, 2005, A6, a urokinase plasminogen activator (uPA)-derived peptide in patients with advanced gynecologic cancer: a phase I trial, Gynecol. Oncol., 99, 50, 10.1016/j.ygyno.2005.05.023

Bilder, 2000, Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors, Science, 289, 113, 10.1126/science.289.5476.113

Biondi, 2000, MMP1 and MMP3 polymorphisms in promoter regions and cancer, Clin. Chem., 46, 2023, 10.1093/clinchem/46.12.2023

Bird, 2000, Exercise-induced changes in proteoglycan metabolism of equine articular cartilage, Equine Vet. J., 32, 161, 10.2746/042516400777591624

Birk, 2005, Collagen Suprastructures, Top. Curr. Biol., 247, 185

Bissell, 2001, Putting tumours in context, Nat. Rev. Cancer, 1, 46, 10.1038/35094059

Boyd, 2002, Heritability of mammographic density, a risk factor for breast cancer, N. Engl. J. Med., 347, 886, 10.1056/NEJMoa013390

Boyd, 2007, Mammographic density and the risk and detection of breast cancer, N. Engl. J. Med., 356, 227, 10.1056/NEJMoa062790

Brown, 2003, Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation, Nat. Med., 9, 796, 10.1038/nm879

Bunn, 1978, The glycosylation of hemoglobin: relevance to diabetes mellitus, Science, 200, 21, 10.1126/science.635569

Butcher, 2009, A tense situation: forcing tumour progression, Nat. Rev. Cancer, 9, 108, 10.1038/nrc2544

Cattell, 1996, Age-related changes in amounts and concentrations of collagen and elastin in normotensive human thoracic aorta, Clin. Chim. Acta, 245, 73, 10.1016/0009-8981(95)06174-6

Chakraborti, 2003, Regulation of matrix metalloproteinases: an overview, Mol. Cell. Biochem., 253, 269, 10.1023/A:1026028303196

Chlenski, 2010, Modulation of matrix remodeling by SPARC in neoplastic progression, Semin. Cell Dev. Biol., 21, 55, 10.1016/j.semcdb.2009.11.018

Condeelis, 2006, Macrophages: obligate partners for tumor cell migration, invasion, and metastasis, Cell, 124, 263, 10.1016/j.cell.2006.01.007

Condeelis, 2003, Intravital imaging of cell movement in tumours, Nat. Rev. Cancer, 3, 921, 10.1038/nrc1231

Cortese, 2009, Mechanical gradient cues for guided cell motility and control of cell behavior on uniform substrates, Adv. Funct. Mater., 19, 2961, 10.1002/adfm.200900918

Coussens, 2001, Inflammatory cells and cancer: think different!, J. Exp. Med., 193, F23, 10.1084/jem.193.6.F23

Coussens, 2002, Matrix metalloproteinase inhibitors and cancer: trials and tribulations, Science, 295, 2387, 10.1126/science.1067100

Csiszar, 2001, Lysyl oxidases: a novel multifunctional amine oxidase family, Prog. Nucleic Acid Res. Mol. Biol., 70, 1, 10.1016/S0079-6603(01)70012-8

Denton, 2001, Transforming growth factor-beta and connective tissue growth factor: key cytokines in scleroderma pathogenesis, Curr. Opin. Rheumatol., 13, 505, 10.1097/00002281-200111000-00010

Derda, 2009, Paper-supported 3D cell culture for tissue-based bioassays, Proc. Natl. Acad. Sci. USA, 106, 18457, 10.1073/pnas.0910666106

Desgrosellier, 2010, Integrins in cancer: biological implications and therapeutic opportunities, Nat. Rev. Cancer, 10, 9, 10.1038/nrc2748

Discher, 2009, Growth factors, matrices, and forces combine and control stem cells, Science, 324, 1673, 10.1126/science.1171643

Dror, 1999, Shwachman-Diamond syndrome: an inherited preleukemic bone marrow failure disorder with aberrant hematopoietic progenitors and faulty marrow microenvironment, Blood, 94, 3048, 10.1182/blood.V94.9.3048

Dufour, 2008, Role of the hemopexin domain of matrix metalloproteinases in cell migration, J. Cell. Physiol., 217, 643, 10.1002/jcp.21535

Durier, 2003, Physiological genomics of human arteries: quantitative relationship between gene expression and arterial stiffness, Circulation, 108, 1845, 10.1161/01.CIR.0000091407.86925.7A

Ebihara, 2000, Changes in extracellular matrix and tissue viscoelasticity in bleomycin-induced lung fibrosis. Temporal aspects, Am. J. Respir. Crit. Care Med., 162, 1569, 10.1164/ajrccm.162.4.9912011

Egeblad, 2002, New functions for the matrix metalloproteinases in cancer progression, Nat. Rev. Cancer, 2, 161, 10.1038/nrc745

Engel, 1987, Calcium binding domains and calcium-induced conformational transition of SPARC/BM-40/osteonectin, an extracellular glycoprotein expressed in mineralized and nonmineralized tissues, Biochemistry, 26, 6958, 10.1021/bi00396a015

Engler, 2006, Matrix elasticity directs stem cell lineage specification, Cell, 126, 677, 10.1016/j.cell.2006.06.044

Erler, 2008, The cellular microenvironment and metastases, Abeloff’s Clinical Oncology, Fourth Edition, 33

Erler, 2010, Network-based drugs and biomarkers, J. Pathol., 220, 290, 10.1002/path.2646

Erler, 2009, Three-dimensional context regulation of metastasis, Clin. Exp. Metastasis, 26, 35, 10.1007/s10585-008-9209-8

Erler, 2006, Lysyl oxidase is essential for hypoxia-induced metastasis, Nature, 440, 1222, 10.1038/nature04695

Erler, 2009, Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche, Cancer Cell, 15, 35, 10.1016/j.ccr.2008.11.012

Frank, 1991, On the pathogenesis of diabetic retinopathy. A 1990 update, Ophthalmology, 98, 586, 10.1016/S0161-6420(91)32253-X

Friedman, 2004, Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications, Nat. Clin. Pract. Gastroenterol. Hepatol., 1, 98, 10.1038/ncpgasthep0055

Friedman, 2000, Mechanisms and therapy of hepatic fibrosis: report of the AASLD single topic basic research conference, Hepatology, 32, 1403, 10.1053/jhep.2000.20243

Funk, 1991, The Ca2(+)-binding glycoprotein SPARC modulates cell cycle progression in bovine aortic endothelial cells, Proc. Natl. Acad. Sci. USA, 88, 2648, 10.1073/pnas.88.7.2648

Giampieri, 2009, Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility, Nat. Cell Biol., 11, 1287, 10.1038/ncb1973

Giancotti, 1999, Integrin signaling, Science, 285, 1028, 10.1126/science.285.5430.1028

Glasheen, 2009, Distinct functions for the catalytic and hemopexin domains of a Drosophila matrix metalloproteinase, Proc. Natl. Acad. Sci. USA, 106, 2659, 10.1073/pnas.0804171106

Glenn, 2009, The role of advanced glycation end products in retinal ageing and disease, Biochim. Biophys. Acta, 1790, 1109, 10.1016/j.bbagen.2009.04.016

Goffin, 2005, Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer, Clin. Cancer Res., 11, 3417, 10.1158/1078-0432.CCR-04-2144

Graham, 2010, Tissue section AFM: In situ ultrastructural imaging of native biomolecules, Matrix Biol., 29, 254, 10.1016/j.matbio.2010.01.008

Gueta, 2006, Measurement of the mechanical properties of isolated tectorial membrane using atomic force microscopy, Proc. Natl. Acad. Sci. USA, 103, 14790, 10.1073/pnas.0603429103

Hadjipanayi, 2009, Guiding cell migration in 3D: a collagen matrix with graded directional stiffness, Cell Motil. Cytoskeleton, 66, 121, 10.1002/cm.20331

Hasegawa, 2005, Pathogenesis of systemic sclerosis: altered B cell function is the key linking systemic autoimmunity and tissue fibrosis, J. Dermatol. Sci., 39, 1, 10.1016/j.jdermsci.2005.03.013

Hicke, 2006, Tumor targeting by an aptamer, J. Nucl. Med., 47, 668

Hornstra, 2003, Lysyl oxidase is required for vascular and diaphragmatic development in mice, J. Biol. Chem., 278, 14387, 10.1074/jbc.M210144200

Hynes, 2009, The extracellular matrix: not just pretty fibrils, Science, 326, 1216, 10.1126/science.1176009

Ingman, 2006, Macrophages promote collagen fibrillogenesis around terminal end buds of the developing mammary gland, Dev. Dyn., 235, 3222, 10.1002/dvdy.20972

Iredale, 2007, Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ, J. Clin. Invest., 117, 539, 10.1172/JCI30542

Issa, 2004, Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking, Gastroenterology, 126, 1795, 10.1053/j.gastro.2004.03.009

Jacobs, 1999, Radial scars in benign breast-biopsy specimens and the risk of breast cancer, N. Engl. J. Med., 340, 430, 10.1056/NEJM199902113400604

Jiang, 2004, Tumor imaging by means of proteolytic activation of cell-penetrating peptides, Proc. Natl. Acad. Sci. USA, 101, 17867, 10.1073/pnas.0408191101

Jodele, 2006, Modifying the soil to affect the seed: role of stromal-derived matrix metalloproteinases in cancer progression, Cancer Metastasis Rev., 25, 35, 10.1007/s10555-006-7887-8

Kagan, 1994, Lysyl oxidase: mechanism, regulation and relationship to liver fibrosis, Pathol. Res. Pract., 190, 910, 10.1016/S0344-0338(11)80995-7

Kagan, 2000, Intra- and extracellular enzymes of collagen biosynthesis as biological and chemical targets in the control of fibrosis, Acta Trop., 77, 147, 10.1016/S0001-706X(00)00128-5

Kagan, 2003, Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell, J. Cell. Biochem., 88, 660, 10.1002/jcb.10413

Kaler, 1994, Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus, Nat. Genet., 8, 195, 10.1038/ng1094-195

Kaplan, 2005, VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche, Nature, 438, 820, 10.1038/nature04186

Kass, 2007, Mammary epithelial cell: influence of extracellular matrix composition and organization during development and tumorigenesis, Int. J. Biochem. Cell Biol., 39, 1987, 10.1016/j.biocel.2007.06.025

Kaviratne, 2004, IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent, J. Immunol., 173, 4020, 10.4049/jimmunol.173.6.4020

Keeley, 2009, Fibrocytes: Bringing new insights into mechanisms of inflammation and fibrosis, Int. J. Biochem. Cell Biol., 42, 535, 10.1016/j.biocel.2009.10.014

Kessenbrock, 2010, Matrix metalloproteinases: regulators of the tumor microenvironment, Cell, 141, 52, 10.1016/j.cell.2010.03.015

Kirschmann, 2002, A molecular role for lysyl oxidase in breast cancer invasion, Cancer Res., 62, 4478

Klotzsch, 2009, Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites, Proc. Natl. Acad. Sci. USA, 106, 18267, 10.1073/pnas.0907518106

Korosoglou, 2008, Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using “positive contrast” magnetic resonance imaging, J. Am. Coll. Cardiol., 52, 483, 10.1016/j.jacc.2008.03.063

Kumar, 2009, Mechanics, malignancy, and metastasis: the force journey of a tumor cell, Cancer Metastasis Rev., 28, 113, 10.1007/s10555-008-9173-4

Lane, 1994, The biology of SPARC, a protein that modulates cell-matrix interactions, FASEB J., 8, 163, 10.1096/fasebj.8.2.8119487

Le, 2007, Expression and prognostic significance of a panel of tissue hypoxia markers in head-and-neck squamous cell carcinomas, Int. J. Radiat. Oncol. Biol. Phys., 69, 167, 10.1016/j.ijrobp.2007.01.071

Le, 2009, Validation of lysyl oxidase as a prognostic marker for metastasis and survival in head and neck squamous cell carcinoma: radiation therapy oncology group trial 90–03, J. Clin. Oncol., 27, 4281, 10.1200/JCO.2008.20.6003

Levental, 2009, Matrix crosslinking forces tumor progression by enhancing integrin signaling, Cell, 139, 891, 10.1016/j.cell.2009.10.027

Li, 1997, Overexpression of transforming growth factor-beta1 and insulin-like growth factor-I in patients with idiopathic hypertrophic cardiomyopathy, Circulation, 96, 874, 10.1161/01.CIR.96.3.874

Littlepage, 2010, Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression, Cancer Res., 70, 2224, 10.1158/0008-5472.CAN-09-3515

Lo, 2000, Cell movement is guided by the rigidity of the substrate, Biophys. J., 79, 144, 10.1016/S0006-3495(00)76279-5

Low, 2006, Technology Insight: optical coherence tomography-current status and future development, Nat. Clin. Pract. Cardiovasc. Med., 3, 154, 10.1038/ncpcardio0482

Mack, 2010, Lost in migration, Nat. Biotechnol., 28, 214, 10.1038/nbt0310-214

Maki, 2002, Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice, Circulation, 106, 2503, 10.1161/01.CIR.0000038109.84500.1E

Markiewicz, 2004, The 72-kilodalton IE-1 protein of human cytomegalovirus (HCMV) is a potent inducer of connective tissue growth factor (CTGF) in human dermal fibroblasts, Clin. Exp. Rheumatol., 22, S31

Massague, 2008, TGFbeta in Cancer, Cell, 134, 215, 10.1016/j.cell.2008.07.001

McAteer, 2008, Magnetic resonance imaging of endothelial adhesion molecules in mouse atherosclerosis using dual-targeted microparticles of iron oxide, Arterioscler. Thromb. Vasc. Biol., 28, 77, 10.1161/ATVBAHA.107.145466

McPhail, 2010, Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors: relationship to histologic assessment of hypoxia and fibrosis, Radiology, 254, 110, 10.1148/radiol.2541090395

Michigami, 2000, Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and alpha(4)beta(1)-integrin enhances production of osteoclast-stimulating activity, Blood, 96, 1953, 10.1182/blood.V96.5.1953

Miserus, 2009, Molecular MRI of early thrombus formation using a bimodal alpha2-antiplasmin-based contrast agent, JACC Cardiovasc. Imaging, 2, 987, 10.1016/j.jcmg.2009.03.015

Mitsiades, 2001, Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity, Cancer Res., 61, 577

Moore, 2005, CCR2-mediated recruitment of fibrocytes to the alveolar space after fibrotic injury, Am. J. Pathol., 166, 675, 10.1016/S0002-9440(10)62289-4

Morikawa, 1988, Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice, Cancer Res., 48, 6863

Mosher, 1979, Cross-linking of fibronectin to collagen by blood coagulation Factor XIIIa, J. Clin. Invest., 64, 781, 10.1172/JCI109524

Mosher, 1979, Inhibition of blood coagulation factor XIIIa-mediated cross-linking between fibronectin and collagen by polyamines, J. Supramol. Struct., 11, 227, 10.1002/jss.400110212

Mossman, 1998, Mechanisms in the pathogenesis of asbestosis and silicosis, Am. J. Respir. Crit. Care Med., 157, 1666, 10.1164/ajrccm.157.5.9707141

Mott, 2004, Regulation of matrix biology by matrix metalloproteinases, Curr. Opin. Cell Biol., 16, 558, 10.1016/j.ceb.2004.07.010

Moustakas, 2005, Non-Smad TGF-beta signals, J. Cell Sci., 118, 3573, 10.1242/jcs.02554

Murawaki, 1991, Serum lysyl oxidase activity in chronic liver disease in comparison with serum levels of prolyl hydroxylase and laminin, Hepatology, 14, 1167, 10.1002/hep.1840140635

Murphy-Ullrich, 1995, SPARC mediates focal adhesion disassembly in endothelial cells through a follistatin-like region and the Ca(2+)-binding EF-hand, J. Cell. Biochem., 57, 341, 10.1002/jcb.240570218

Muthuswamy, 2001, ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini, Nat. Cell Biol., 3, 785, 10.1038/ncb0901-785

Oldberg, 2007, Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinoma, Proc. Natl. Acad. Sci. USA, 104, 13966, 10.1073/pnas.0702014104

Pampaloni, 2007, The third dimension bridges the gap between cell culture and live tissue, Nat. Rev. Mol. Cell Biol., 8, 839, 10.1038/nrm2236

Pardo, 2006, Matrix metalloproteases in aberrant fibrotic tissue remodeling, Proc. Am. Thorac. Soc., 3, 383, 10.1513/pats.200601-012TK

Paszek, 2004, The tension mounts: mechanics meets morphogenesis and malignancy, J. Mammary Gland Biol. Neoplasia, 9, 325, 10.1007/s10911-004-1404-x

Paszek, 2005, Tensional homeostasis and the malignant phenotype, Cancer Cell, 8, 241, 10.1016/j.ccr.2005.08.010

Pawson, 2008, Network medicine, FEBS Lett., 582, 1266, 10.1016/j.febslet.2008.02.011

Payne, 2005, Lysyl oxidase regulates breast cancer cell migration and adhesion through a hydrogen peroxide-mediated mechanism, Cancer Res., 65, 11429, 10.1158/0008-5472.CAN-05-1274

Payne, 2007, Paradoxical roles for lysyl oxidases in cancer-a prospect, J. Cell. Biochem., 101, 1338, 10.1002/jcb.21371

Perentes, 2009, In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblasts, Nat. Methods, 6, 143, 10.1038/nmeth.1295

Phillips, 2004, Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis, J. Clin. Invest., 114, 438, 10.1172/JCI200420997

Provenzano, 2006, Collagen reorganization at the tumor-stromal interface facilitates local invasion, BMC Med., 4, 38, 10.1186/1741-7015-4-38

Provenzano, 2008, Collagen density promotes mammary tumor initiation and progression, BMC Med., 6, 11, 10.1186/1741-7015-6-11

Radermacher, 2009, In vivo detection of inflammation using pegylated iron oxide particles targeted at E-selectin: a multimodal approach using MR imaging and EPR spectroscopy, Invest. Radiol., 44, 398, 10.1097/RLI.0b013e3181a49639

Radisky, 2001, Tumors are unique organs defined by abnormal signaling and context, Semin. Cancer Biol., 11, 87, 10.1006/scbi.2000.0360

Reardon, 2008, A pilot study: 131I-antitenascin monoclonal antibody 81c6 to deliver a 44-Gy resection cavity boost, Neuro. Oncol., 10, 182, 10.1215/15228517-2007-053

Reynolds, 2006, Detection of vascular expression of E-selectin in vivo with MR imaging, Radiology, 241, 469, 10.1148/radiol.2412050490

Rittweger, 2006, Bone loss from the human distal tibia epiphysis during 24 days of unilateral lower limb suspension, J. Physiol., 577, 331, 10.1113/jphysiol.2006.115782

Rittweger, 2009, Bone loss in the lower leg during 35 days of bed rest is predominantly from the cortical compartment, Bone, 44, 612, 10.1016/j.bone.2009.01.001

Rocco, 2001, Lung tissue mechanics and extracellular matrix remodeling in acute lung injury, Am. J. Respir. Crit. Care Med., 164, 1067, 10.1164/ajrccm.164.6.2007062

Rosenbaum, 2005, Marimastat in the treatment of patients with biochemically relapsed prostate cancer: a prospective randomized, double-blind, phase I/II trial, Clin. Cancer Res., 11, 4437, 10.1158/1078-0432.CCR-04-2252

Rosenkranz, 2002, Alterations of beta-adrenergic signaling and cardiac hypertrophy in transgenic mice overexpressing TGF-beta(1), Am. J. Physiol. Heart Circ. Physiol., 283, H1253, 10.1152/ajpheart.00578.2001

Roskelley, 1995, A hierarchy of ECM-mediated signalling regulates tissue-specific gene expression, Curr. Opin. Cell Biol., 7, 736, 10.1016/0955-0674(95)80117-0

Royce, 1980, Reduced lysyl oxidase activity in skin fibroblasts from patients with Menkes’ syndrome, Biochem. J., 192, 579, 10.1042/bj1920579

Roycik, 2009, A fresh prospect of extracellular matrix hydrolytic enzymes and their substrates, Curr. Pharm. Des., 15, 1295, 10.2174/138161209787846676

Sage, 1984, Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture, J. Biol. Chem., 259, 3993, 10.1016/S0021-9258(17)43194-2

Sage, 1989, SPARC, a secreted protein associated with cellular proliferation, inhibits cell spreading in vitro and exhibits Ca+2-dependent binding to the extracellular matrix, J. Cell Biol., 109, 341, 10.1083/jcb.109.1.341

Sakamoto, 2009, Cytoplasmic tail of MT1-MMP regulates macrophage motility independently from its protease activity, Genes Cells, 14, 617, 10.1111/j.1365-2443.2009.01293.x

Sasaki, 1998, Advanced glycation end products in Alzheimer’s disease and other neurodegenerative diseases, Am. J. Pathol., 153, 1149, 10.1016/S0002-9440(10)65659-3

Scherer, 2008, Imaging matrix metalloproteinases in cancer, Cancer Metastasis Rev., 27, 679, 10.1007/s10555-008-9152-9

Scherer, 2008, Optical imaging of matrix metalloproteinase-7 activity in vivo using a proteolytic nanobeacon, Mol. Imaging, 7, 118, 10.2310/7290.2008.00010

Schmeichel, 2003, Modeling tissue-specific signaling and organ function in three dimensions, J. Cell Sci., 116, 2377, 10.1242/jcs.00503

Schnider, 1980, Glucosylation of human collagen in aging and diabetes mellitus, J. Clin. Invest., 66, 1179, 10.1172/JCI109950

Schwartz, 1999, Interactions between mitogenic stimuli, or, a thousand and one connections, Curr. Opin. Cell Biol., 11, 197, 10.1016/S0955-0674(99)80026-X

Sethi, 1999, Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo, Nat. Med., 5, 662, 10.1038/9511

Sherratt, 2003, Fibrillin microfibrils are stiff reinforcing fibres in compliant tissues, J. Mol. Biol., 332, 183, 10.1016/S0022-2836(03)00829-5

Sivakumar, 2008, Upregulation of lysyl oxidase and MMPs during cardiac remodeling in human dilated cardiomyopathy, Mol. Cell. Biochem., 307, 159, 10.1007/s11010-007-9595-2

Sivan, 2008, Collagen turnover in normal and degenerate human intervertebral discs as determined by the racemization of aspartic acid, J. Biol. Chem., 283, 8796, 10.1074/jbc.M709885200

Spuentrup, 2005, Molecular magnetic resonance imaging of coronary thrombosis and pulmonary emboli with a novel fibrin-targeted contrast agent, Circulation, 111, 1377, 10.1161/01.CIR.0000158478.29668.9B

Sternlicht, 2001, How matrix metalloproteinases regulate cell behavior, Annu. Rev. Cell Dev. Biol., 17, 463, 10.1146/annurev.cellbio.17.1.463

Sternlicht, 1999, The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis, Cell, 98, 137, 10.1016/S0092-8674(00)81009-0

Stover, 2007, A delicate balance: TGF-beta and the tumor microenvironment, J. Cell. Biochem., 101, 851, 10.1002/jcb.21149

Stracke, 2007, Molecular MRI of cerebral venous sinus thrombosis using a new fibrin-specific MR contrast agent, Stroke, 38, 1476, 10.1161/STROKEAHA.106.479998

Strieter, 2007, The role of CXC chemokines in pulmonary fibrosis, J. Clin. Invest., 117, 549, 10.1172/JCI30562

Strongin, 2006, Mislocalization and unconventional functions of cellular MMPs in cancer, Cancer Metastasis Rev., 25, 87, 10.1007/s10555-006-7892-y

Suki, 2008, Extracellular matrix mechanics in lung parenchymal diseases, Respir. Physiol. Neurobiol., 163, 33, 10.1016/j.resp.2008.03.015

Termine, 1981, Mineral and collagen-binding proteins of fetal calf bone, J. Biol. Chem., 256, 10403, 10.1016/S0021-9258(19)68633-3

Tsien, 2005, Building and breeding molecules to spy on cells and tumors, FEBS Lett., 579, 927, 10.1016/j.febslet.2004.11.025

Varga, 2007, Systemic sclerosis: a prototypic multisystem fibrotic disorder, J. Clin. Invest., 117, 557, 10.1172/JCI31139

Vaupel, 1989, Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review, Cancer Res., 49, 6449

Verzijl, 2000, Effect of collagen turnover on the accumulation of advanced glycation end products, J. Biol. Chem., 275, 39027, 10.1074/jbc.M006700200

Vitek, 1994, Advanced glycation end products contribute to amyloidosis in Alzheimer disease, Proc. Natl. Acad. Sci. USA, 91, 4766, 10.1073/pnas.91.11.4766

Watanabe, 2005, Angiotensin II and the endothelium: diverse signals and effects, Hypertension, 45, 163, 10.1161/01.HYP.0000153321.13792.b9

Weaver, 1996, The importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay, Biochem. Cell Biol., 74, 833, 10.1139/o96-089

Weaver, 1997, Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies, J. Cell Biol., 137, 231, 10.1083/jcb.137.1.231

Wells, 2008, Matrix elasticity, cytoskeletal tension, and TGF-beta: the insoluble and soluble meet, Sci. Signal., 1, e13, 10.1126/stke.110pe13

Wiberg, 2003, Complexes of matrilin-1 and biglycan or decorin connect collagen VI microfibrils to both collagen II and aggrecan, J. Biol. Chem., 278, 37698, 10.1074/jbc.M304638200

Wipff, 2007, Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix, J. Cell Biol., 179, 1311, 10.1083/jcb.200704042

Wolf, 2009, Collagen-based cell migration models in vitro and in vivo, Semin. Cell Dev. Biol., 20, 931, 10.1016/j.semcdb.2009.08.005

Wolfe, 1976, Risk for breast cancer development determined by mammographic parenchymal pattern, Cancer, 37, 2486, 10.1002/1097-0142(197605)37:5<2486::AID-CNCR2820370542>3.0.CO;2-8

Wolfe, 1976, Breast patterns as an index of risk for developing breast cancer, AJR Am. J. Roentgenol., 126, 1130, 10.2214/ajr.126.6.1130

Wong, 2003, Directed movement of vascular smooth muscle cells on gradient-compliant hydrogels, Langmuir, 19, 1908, 10.1021/la026403p

Wynn, 2007, Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases, J. Clin. Invest., 117, 524, 10.1172/JCI31487

Yamada, 2007, Modeling tissue morphogenesis and cancer in 3D, Cell, 130, 601, 10.1016/j.cell.2007.08.006

Yu, 2010, Forcing form and function: biomechanical regulation of tumor evolution, Trends Cell Biol., 21, 47, 10.1016/j.tcb.2010.08.015