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Journal of Mammary Gland Biology and Neoplasia

Published in:

01-06-2011

Choreographing Metastasis to the Tune of LTBP

Authors: Anupama Chandramouli, Julia Simundza, Alicia Pinderhughes, Pamela Cowin

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 2/2011

Abstract

Latent Transforming Growth Factor beta (TGFβ) Binding Proteins (LTBPs) are chaperones and determinants of TGFβ isoform-specific secretion. They belong to the LTBP/Fibrillin family and form integral components of the fibronectin and microfibrillar extracellular matrix (ECM). LTBPs serve as master regulators of TGFβ bioavailability, functioning to incorporate and spatially pattern latent TGFβ at regular intervals within the ECM, and actively participate in integrin-mediated stretch activation of TGFβ in vivo. In so doing they create a highly patterned sensory system where local changes in ECM tension can be detected and transduced into focal signals. The physiological role of LTBPs in the mammary gland remains largely unstudied, however both loss and gain of LTBP expression is found in breast cancers and breast cancer cell lines. Importantly, elevated LTBP1 levels appear in two gene signatures predictive of enhanced metastatic behavior. LTBP may promote metastasis by providing the bridge between structural and signaling components of the epithelial to mesenchymal transition (EMT).

Gorska AE, Joseph H, Derynck R, Moses HL, Serra R. Dominant-negative interference of the transforming growth factor beta type II receptor in mammary gland epithelium results in alveolar hyperplasia and differentiation in virgin mice. Cell Growth Differ. 1998;9(3):229–38.PubMed

Hyytiainen M, Penttinen C, Keski-Oja J. Latent TGF-beta binding proteins: extracellular matrix association and roles in TGF-beta activation. Crit Rev Clin Lab Sci. 2004;41(3):233–64.PubMed

Ewan KB, Shyamala G, Ravani SA, et al. Latent transforming growth factor-beta activation in mammary gland: regulation by ovarian hormones affects ductal and alveolar proliferation. Am J Pathol. 2002;160(6):2081–93.PubMed

Robinson SD, Silberstein GB, Roberts AB, Flanders KC, Daniel CW. Regulated expression and growth inhibitory effects of transforming growth factor-beta isoforms in mouse mammary gland development. Development. 1991;113(3):867–78.PubMed

Joseph H, Gorska AE, Sohn P, Moses HL, Serra R. Overexpression of a kinase-deficient transforming growth factor-beta type II receptor in mouse mammary stroma results in increased epithelial branching. Mol Biol Cell. 1999;10(4):1221–34.PubMed

Roarty K, Serra R. Wnt5a is required for proper mammary gland development and TGF-beta-mediated inhibition of ductal growth. Development. 2007;134(21):3929–39.PubMed

Bottinger EP, Jakubczak JL, Roberts IS, et al. Expression of a dominant-negative mutant TGF-beta type II receptor in transgenic mice reveals essential roles for TGF-beta in regulation of growth and differentiation in the exocrine pancreas. EMBO J. 1997;16(10):2621–33.PubMed

Lenferink AE, Magoon J, Pepin MC, Guimond A, O’Connor-McCourt MD. Expression of TGF-beta type II receptor antisense RNA impairs TGF-beta signaling in vitro and promotes mammary gland differentiation in vivo. Int J Cancer. 2003;107(6):919–28.PubMed

Nguyen AV, Pollard JW. Transforming growth factor beta3 induces cell death during the first stage of mammary gland involution. Development. 2000;127(14):3107–18.PubMed

10.

Pierce Jr DF, Johnson MD, Matsui Y, et al. Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1. Genes Dev. 1993;7(12A):2308–17.PubMed

11.

Jhappan C, Geiser AG, Kordon EC, et al. Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation. EMBO J. 1993;12(5):1835–45.PubMed

12.

Kordon EC, McKnight RA, Jhappan C, Hennighausen L, Merlino G, Smith GH. Ectopic TGF beta 1 expression in the secretory mammary epithelium induces early senescence of the epithelial stem cell population. Dev Biol. 1995;168(1):47–61.PubMed

13.

Muraoka-Cook RS, Shin I, Yi JY, et al. Activated type I TGFbeta receptor kinase enhances the survival of mammary epithelial cells and accelerates tumor progression. Oncogene. 2006;25(24):3408–23.PubMed

14.

Moses H, Barcellos-Hoff MH. TGF-{beta} Biology in Mammary Development and Breast Cancer. Cold Spring Harb Perspect Biol. Sep 1.

15.

Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704–15.PubMed

16.

Barcellos-Hoff MH. Radiation-induced transforming growth factor beta and subsequent extracellular matrix reorganization in murine mammary gland. Cancer Res. 1993;53(17):3880–6.PubMed

17.

Barcellos-Hoff MH. Latency and activation in the control of TGF-beta. J Mammary Gland Biol Neoplasia. 1996;1(4):353–63.

18.

Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. J Cell Sci. 2003;116(Pt 2):217–24.PubMed

19.

Miyazono K, Hellman U, Wernstedt C, Heldin CH. Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization. J Biol Chem. 1988;263(13):6407–15.PubMed

20.

Miyazono K, Olofsson A, Colosetti P, Heldin CH. A role of the latent TGF-beta 1-binding protein in the assembly and secretion of TGF-beta 1. EMBO J. 1991;10(5):1091–101.PubMed

21.

Gleizes PE, Beavis RC, Mazzieri R, Shen B, Rifkin DB. Identification and characterization of an eight-cysteine repeat of the latent transforming growth factor-beta binding protein-1 that mediates bonding to the latent transforming growth factor-beta1. J Biol Chem. 1996;271(47):29891–6.PubMed

22.

Lack J, O’Leary JM, Knott V, et al. Solution structure of the third TB domain from LTBP1 provides insight into assembly of the large latent complex that sequesters latent TGF-beta. J Mol Biol. 2003;334(2):281–91.PubMed

23.

Walton KL, Makanji Y, Chen J, et al. Two distinct regions of latency-associated peptide coordinate stability of the latent transforming growth factor-beta1 complex. J Biol Chem. 2010;285(22):17029–37.PubMed

24.

Miyazono K, Thyberg J, Heldin CH. Retention of the transforming growth factor-beta 1 precursor in the Golgi complex in a latent endoglycosidase H-sensitive form. J Biol Chem. 1992;267(8):5668–75.PubMed

25.

Gentry LE, Lioubin MN, Purchio AF, Marquardt H. Molecular events in the processing of recombinant type 1 pre-pro-transforming growth factor beta to the mature polypeptide. Mol Cell Biol. 1988;8(10):4162–8.PubMed

26.

Brunner AM, Marquardt H, Malacko AR, Lioubin MN, Purchio AF. Site-directed mutagenesis of cysteine residues in the pro region of the transforming growth factor beta 1 precursor. Expression and characterization of mutant proteins. J Biol Chem. 1989;264(23):13660–4.PubMed

27.

Robertson I, Jensen S, Handford P. TB doman proteins: evolutionary insights into the multifaceted roles of fibrillins and LTBPs. Biochem J. 2011;433:263–76.PubMed

28.

Tsuji T, Okada F, Yamaguchi K, Nakamura T. Molecular cloning of the large subunit of transforming growth factor type beta masking protein and expression of the mRNA in various rat tissues. Proc Natl Acad Sci USA. 1990;87(22):8835–9.PubMed

29.

Kanzaki T, Olofsson A, Moren A, et al. TGF-beta 1 binding protein: a component of the large latent complex of TGF-beta 1 with multiple repeat sequences. Cell. 1990;61(6):1051–61.PubMed

30.

Moren A, Olofsson A, Stenman G, et al. Identification and characterization of LTBP-2, a novel latent transforming growth factor-beta-binding protein. J Biol Chem. 1994;269(51):32469–78.PubMed

31.

Yin W, Smiley E, Germiller J, et al. Isolation of a novel latent transforming growth factor-beta binding protein gene (LTBP-3). J Biol Chem. 1995;270(17):10147–60.PubMed

32.

Giltay R, Kostka G, Timpl R. Sequence and expression of a novel member (LTBP-4) of the family of latent transforming growth factor-beta binding proteins. FEBS Lett. 1997;411(2–3):164–8.PubMed

33.

Saharinen J, Keski-Oja J. Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates a hydrophobic interaction surface for binding of small latent TGF-beta. Mol Biol Cell. 2000;11(8):2691–704.PubMed

34.

Chen Y, Ali T, Todorovic V, O’Leary JM, Kristina Downing A, Rifkin DB. Amino acid requirements for formation of the TGF-beta-latent TGF-beta binding protein complexes. J Mol Biol. 2005;345(1):175–86.PubMed

35.

Gibson MA, Hatzinikolas G, Davis EC, Baker E, Sutherland GR, Mecham RP. Bovine latent transforming growth factor beta 1-binding protein 2: molecular cloning, identification of tissue isoforms, and immunolocalization to elastin-associated microfibrils. Mol Cell Biol. 1995;15(12):6932–42.PubMed

36.

Taipale J, Saharinen J, Hedman K, Keski-Oja J. Latent transforming growth factor-beta 1 and its binding protein are components of extracellular matrix microfibrils. J Histochem Cytochem. 1996;44(8):875–89.PubMed

37.

Kantola AK, Keski-Oja J, Koli K. Fibronectin and heparin binding domains of latent TGF-beta binding protein (LTBP)-4 mediate matrix targeting and cell adhesion. Exp Cell Res. 2008;314(13):2488–500.PubMed

38.

Ramirez F, Sakai LY. Biogenesis and function of fibrillin assemblies. Cell Tissue Res. 2010;339(1):71–82.PubMed

39.

Sakai LY, Keene DR, Glanville RW, Bachinger HP. Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. J Biol Chem. 1991;266(22):14763–70.PubMed

40.

Sakai LY, Keene DR, Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol. 1986;103(6 Pt 1):2499–509.PubMed

41.

Kielty CM, Baldock C, Lee D, Rock MJ, Ashworth JL, Shuttleworth CA. Fibrillin: from microfibril assembly to biomechanical function. Philos Trans R Soc Lond B Biol Sci. 2002;357(1418):207–17.PubMed

42.

Lu Y, Holmes DF, Baldock C. Evidence for the intramolecular pleating model of fibrillin microfibril organisation from single particle image analysis. J Mol Biol. 2005;349(1):73–85.PubMed

43.

Ramirez F, Rifkin DB. Extracellular microfibrils: contextual platforms for TGFbeta and BMP signaling. Curr Opin Cell Biol. 2009;21(5):616–22.PubMed

44.

Nunes I, Gleizes PE, Metz CN, Rifkin DB. Latent transforming growth factor-beta binding protein domains involved in activation and transglutaminase-dependent cross-linking of latent transforming growth factor-beta. J Cell Biol. 1997;136(5):1151–63.PubMed

45.

Dallas SL, Sivakumar P, Jones CJ, et al. Fibronectin regulates latent transforming growth factor-beta (TGF beta) by controlling matrix assembly of latent TGF beta-binding protein-1. J Biol Chem. 2005;280(19):18871–80.PubMed

46.

Verderio E, Gaudry C, Gross S, Smith C, Downes S, Griffin M. Regulation of cell surface tissue transglutaminase: effects on matrix storage of latent transforming growth factor-beta binding protein-1. J Histochem Cytochem. 1999;47(11):1417–32.PubMed

47.

Isogai Z, Ono RN, Ushiro S, et al. Latent transforming growth factor beta-binding protein 1 interacts with fibrillin and is a microfibril-associated protein. J Biol Chem. 2003;278(4):2750–7.PubMed

48.

Penttinen C, Saharinen J, Weikkolainen K, Hyytiainen M, Keski-Oja J. Secretion of human latent TGF-beta-binding protein-3 (LTBP-3) is dependent on co-expression of TGF-beta. J Cell Sci. 2002;115(Pt 17):3457–68.PubMed

49.

Brown PD, Wakefield LM, Levinson AD, Sporn MB. Physicochemical activation of recombinant latent transforming growth factor-beta’s 1, 2, and 3. Growth Factors. 1990;3(1):35–43.PubMed

50.

Miyazono K, Heldin CH. Role for carbohydrate structures in TGF-beta 1 latency. Nature. 1989;338(6211):158–60.PubMed

51.

Barcellos-Hoff MH, Dix TA. Redox-mediated activation of latent transforming growth factor-beta 1. Mol Endocrinol. 1996;10(9):1077–83.PubMed

52.

Barcellos-Hoff MH, Derynck R, Tsang ML, Weatherbee JA. Transforming growth factor-beta activation in irradiated murine mammary gland. J Clin Invest. 1994;93(2):892–9.PubMed

53.

Dennis PA, Rifkin DB. Cellular activation of latent transforming growth factor beta requires binding to the cation-independent mannose 6-phosphate/insulin-like growth factor type II receptor. Proc Natl Acad Sci USA. 1991;88(2):580–4.PubMed

54.

Flaumenhaft R, Abe M, Sato Y, et al. Role of the latent TGF-beta binding protein in the activation of latent TGF-beta by co-cultures of endothelial and smooth muscle cells. J Cell Biol. 1993;120(4):995–1002.PubMed

55.

Romer J, Bugge TH, Pyke C, et al. Impaired wound healing in mice with a disrupted plasminogen gene. Nat Med. 1996;2(3):287–92.PubMed

56.

Ge G, Greenspan DS. BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding protein. J Cell Biol. 2006;175(1):111–20.PubMed

57.

Ribeiro SM, Poczatek M, Schultz-Cherry S, Villain M, Murphy-Ullrich JE. The activation sequence of thrombospondin-1 interacts with the latency-associated peptide to regulate activation of latent transforming growth factor-beta. J Biol Chem. 1999;274(19):13586–93.PubMed

58.

Crawford SE, Stellmach V, Murphy-Ullrich JE, et al. Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell. 1998;93(7):1159–70.PubMed

59.

Lawler J, Sunday M, Thibert V, et al. Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. J Clin Invest. 1998;101(5):982–92.PubMed

60.

Munger JS, Sheppard D. Crosstalk among TGFbeta signalling pathways, integrins and the extracellular matrix. Cold Spring Harbor Perspectives. 2011; in press.

61.

Wipff PJ, Hinz B. Integrins and the activation of latent transforming growth factor beta1—an intimate relationship. Eur J Cell Biol. 2008;87(8–9):601–15.PubMed

62.

Lu M, Munger JS, Steadele M, Busald C, Tellier M, Schnapp LM. Integrin alpha8beta1 mediates adhesion to LAP-TGFbeta1. J Cell Sci. 2002;115(Pt 23):4641–8.PubMed

63.

Mu D, Cambier S, Fjellbirkeland L, et al. The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1. J Cell Biol. 2002;157(3):493–507.PubMed

64.

Annes JP, Rifkin DB, Munger JS. The integrin alphaVbeta6 binds and activates latent TGFbeta3. FEBS Lett. 2002;511(1–3):65–8.PubMed

65.

Munger JS, Huang X, Kawakatsu H, et al. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell. 1999;96(3):319–28.PubMed

66.

Munger JS, Harpel JG, Giancotti FG, Rifkin DB. Interactions between growth factors and integrins: latent forms of transforming growth factor-beta are ligands for the integrin alphavbeta1. Mol Biol Cell. 1998;9(9):2627–38.PubMed

67.

Annes JP, Chen Y, Munger JS, Rifkin DB. Integrin alphaVbeta6-mediated activation of latent TGF-beta requires the latent TGF-beta binding protein-1. J Cell Biol. 2004;165(5):723–34.PubMed

68.

Wipff PJ, Rifkin DB, Meister JJ, Hinz B. Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. J Cell Biol. 2007;179(6):1311–23.PubMed

69.

Fjellbirkeland L, Cambier S, Broaddus VC, et al. Integrin alphavbeta8-mediated activation of transforming growth factor-beta inhibits human airway epithelial proliferation in intact bronchial tissue. Am J Pathol. 2003;163(2):533–42.PubMed

70.

Asano Y, Ihn H, Yamane K, Jinnin M, Mimura Y, Tamaki K. Increased expression of integrin alpha(v)beta3 contributes to the establishment of autocrine TGF-beta signaling in scleroderma fibroblasts. J Immunol. 2005;175(11):7708–18.PubMed

71.

Shull MM, Ormsby I, Kier AB, et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature. 1992;359(6397):693–9.PubMed

72.

Kaartinen V, Voncken JW, Shuler C, et al. Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction. Nat Genet. 1995;11(4):415–21.PubMed

73.

Sanford LP, Ormsby I, Gittenberger-de Groot AC, et al. TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. Development. 1997;124(13):2659–70.PubMed

74.

Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ. Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development. 1995;121(6):1845–54.PubMed

75.

Zhu J, Motejlek K, Wang D, Zang K, Schmidt A, Reichardt LF. beta8 integrins are required for vascular morphogenesis in mouse embryos. Development. 2002;129(12):2891–903.PubMed

76.

Aluwihare P, Mu Z, Zhao Z, et al. Mice that lack activity of alphavbeta6- and alphavbeta8-integrins reproduce the abnormalities of Tgfb1- and Tgfb3-null mice. J Cell Sci. 2009;122(Pt 2):227–32.PubMed

77.

Melton AC, Bailey-Bucktrout SL, Travis MA, Fife BT, Bluestone JA, Sheppard D. Expression of alphavbeta8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice. J Clin Invest. 2010;120(12):4436–44.PubMed

78.

Yang Z, Mu Z, Dabovic B, et al. Absence of integrin-mediated TGFbeta1 activation in vivo recapitulates the phenotype of TGFbeta1-null mice. J Cell Biol. 2007;176(6):787–93.PubMed

79.

Araya J, Cambier S, Morris A, Finkbeiner W, Nishimura SL. Integrin-mediated transforming growth factor-beta activation regulates homeostasis of the pulmonary epithelial-mesenchymal trophic unit. Am J Pathol. 2006;169(2):405–15.PubMed

80.

Taddei I, Faraldo MM, Teuliere J, Deugnier MA, Thiery JP, Glukhova MA. Integrins in mammary gland development and differentiation of mammary epithelium. J Mammary Gland Biol Neoplasia. 2003;8(4):383–94.PubMed

81.

Yoshinaga K, Obata H, Jurukovski V, et al. Perturbation of transforming growth factor (TGF)-beta1 association with latent TGF-beta binding protein yields inflammation and tumors. Proc Natl Acad Sci USA. 2008;105(48):18758–63.PubMed

82.

Lee SS, Knott V, Jovanovic J, et al. Structure of the integrin binding fragment from fibrillin-1 gives new insights into microfibril organization. Structure. 2004;12(4):717–29.PubMed

83.

Jovanovic J, Takagi J, Choulier L, et al. alphaVbeta6 is a novel receptor for human fibrillin-1. Comparative studies of molecular determinants underlying integrin-rgd affinity and specificity. J Biol Chem. 2007;282(9):6743–51.PubMed

84.

Jovanovic J, Iqbal S, Jensen S, Mardon H, Handford P. Fibrillin-integrin interactions in health and disease. Biochem Soc Trans. 2008;36(Pt 2):257–62.PubMed

85.

Kinsey R, Williamson MR, Chaudhry S, et al. Fibrillin-1 microfibril deposition is dependent on fibronectin assembly. J Cell Sci. 2008;121(Pt 16):2696–704.PubMed

86.

Pfaff M, Reinhardt DP, Sakai LY, Timpl R. Cell adhesion and integrin binding to recombinant human fibrillin-1. FEBS Lett. 1996;384(3):247–50.PubMed

87.

Mariko B, Ghandour Z, Raveaud S, et al. Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation and migration in human endothelial cells. Am J Physiol Cell Physiol. 2010;299(5):C977–87.PubMed

88.

Noor A, Windpassinger C, Vitcu I, et al. Oligodontia is caused by mutation in LTBP3, the gene encoding latent TGF-beta binding protein 3. Am J Hum Genet. 2009;84(4):519–23.PubMed

89.

Urban Z, Hucthagowder V, Schurmann N, et al. Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. Am J Hum Genet. 2009;85(5):593–605.PubMed

90.

Ali M, McKibbin M, Booth A, et al. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet. 2009;84(5):664–71.PubMed

91.

Todorovic V, Frendewey D, Gutstein DE, et al. Long form of latent TGF-beta binding protein 1 (Ltbp1L) is essential for cardiac outflow tract septation and remodeling. Development. 2007;134(20):3723–32.PubMed

92.

Todorovic V, Finnegan E, Freyer L, Zilberberg L, Ota M, Rifkin DB. Long form of latent TGF-beta binding protein 1 (Ltbp1L) regulates cardiac valve development. Dev Dyn. 240(1):176–87.

93.

Dabovic B, Chen Y, Colarossi C, et al. Bone abnormalities in latent TGF-[beta] binding protein (Ltbp)-3-null mice indicate a role for Ltbp-3 in modulating TGF-[beta] bioavailability. J Cell Biol. 2002;156(2):227–32.PubMed

94.

Colarossi C, Chen Y, Obata H, et al. Lung alveolar septation defects in Ltbp-3-null mice. Am J Pathol. 2005;167(2):419–28.PubMed

95.

Sterner-Kock A, Thorey IS, Koli K, et al. Disruption of the gene encoding the latent transforming growth factor-beta binding protein 4 (LTBP-4) causes abnormal lung development, cardiomyopathy, and colorectal cancer. Genes Dev. 2002;16(17):2264–73.PubMed

96.

Dabovic B, Chen Y, Choi J, et al. Dual functions for LTBP in lung development: LTBP-4 independently modulates elastogenesis and TGF-beta activity. J Cell Physiol. 2009;219(1):14–22.PubMed

97.

Shipley JM, Mecham RP, Maus E, et al. Developmental expression of latent transforming growth factor beta binding protein 2 and its requirement early in mouse development. Mol Cell Biol. 2000;20(13):4879–87.PubMed

98.

Hirai M, Horiguchi M, Ohbayashi T, Kita T, Chien KR, Nakamura T. Latent TGF-beta-binding protein 2 binds to DANCE/fibulin-5 and regulates elastic fiber assembly. EMBO J. 2007;26(14):3283–95.PubMed

99.

Pereira L, Lee SY, Gayraud B, et al. Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1. Proc Natl Acad Sci USA. 1999;96(7):3819–23.PubMed

100.

Mauel S, Kruse B, Etschmann B, et al. Latent transforming growth factor binding protein 4 (LTBP-4) is downregulated in human mammary adenocarcinomas in vitro and in vivo. APMIS. 2007;115(6):687–700.PubMed

101.

Klopfleisch R, Klose P, Gruber AD. The combined expression pattern of BMP2, LTBP4, and DERL1 discriminates malignant from benign canine mammary tumors. Vet Pathol. 2010;47(3):446–54.PubMed

102.

Klopfleisch R, Schutze M, Gruber AD. Downregulation of transforming growth factor beta (TGFbeta) and latent TGFbeta binding protein (LTBP)-4 expression in late stage canine mammary tumours. Vet J. 2010;186(3):379–84.PubMed

103.

Karnoub AE, Dash AB, Vo AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449(7162):557–63.PubMed

104.

Richardson AL, Wang ZC, De Nicolo A, et al. X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell. 2006;9(2):121–32.PubMed

105.

Ramaswamy S, Tamayo P, Rifkin R, et al. Multiclass cancer diagnosis using tumor gene expression signatures. Proc Natl Acad Sci USA. 2001;98(26):15149–54.PubMed

106.

Bos PD, Zhang XH, Nadal C, et al. Genes that mediate breast cancer metastasis to the brain. Nature. 2009;459(7249):1005–9.PubMed

107.

Minn AJ, Gupta GP, Padua D, et al. Lung metastasis genes couple breast tumor size and metastatic spread. Proc Natl Acad Sci USA. 2007;104(16):6740–5.PubMed

108.

Minn AJ, Gupta GP, Siegel PM, et al. Genes that mediate breast cancer metastasis to lung. Nature. 2005;436(7050):518–24.PubMed

109.

Hynes RO. The extracellular matrix: not just pretty fibrils. Science. 2009;326(5957):1216–9.PubMed

110.

Ali IU, Hynes RO. Effects of LETS glycoprotein on cell motility. Cell. 1978;14(2):439–46.PubMed

111.

Puthawala K, Hadjiangelis N, Jacoby SC, et al. Inhibition of integrin αVβ6, an activator of latent TGFβ, prevents radiation-induced lung fibrosis. Am J Respir Crit Care Med. 2008;177(1):82–90.

Title: Choreographing Metastasis to the Tune of LTBP
Authors: Anupama Chandramouli
Julia Simundza
Alicia Pinderhughes
Pamela Cowin
Publication date: 01-06-2011
Publisher: Springer US
Published in: Journal of Mammary Gland Biology and Neoplasia / Issue 2/2011
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI: https://doi.org/10.1007/s10911-011-9215-3

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