Relaxin enhances the collagenolytic activity and in vitro invasiveness by upregulating matrix metalloproteinases in human thyroid carcinoma cells

Molecular Cancer Research

Volumn 9, Issue 6, 2011, Pages 673-687

  Bialek, Joanna ^a   Kunanuvat, Usakorn ^b   Hombach Klonisch, Sabine ^c   Spens, Antje ^a   Stetefeld, Joerg ^c   Sunley, Kevin ^d   Lippert, Dustin ^d   Wilkins, John A ^c,d   Hoang Vu, Cuong ^a   Klonisch, Thomas ^b,c  

^a MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

^b UNIVERSITY OF MANITOBA   (Canada)

^c UNIVERSITY OF MANITOBA   (Canada)

^d UNIVERSITY OF MANITOBA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN; COLLAGENASE 3; ENHANCED GREEN FLUORESCENT PROTEIN; GELATINASE A; GELATINASE B; ILOMASTAT; INTERSTITIAL COLLAGENASE; MATRIX METALLOPROTEINASE 14; NEUTROPHIL COLLAGENASE; RELAXIN; RELAXIN 2; STROMELYSIN; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TISSUE INHIBITOR OF METALLOPROTEINASE 2; TISSUE INHIBITOR OF METALLOPROTEINASE 3; TISSUE INHIBITOR OF METALLOPROTEINASE 4; UNCLASSIFIED DRUG;

ADULT; AGED; AMINO ACID SEQUENCE; ARTICLE; CANCER STAGING; CELL INVASION; COLLAGEN DEGRADATION; CONFOCAL FLUORESCENT MICROSCOPY; CONTROLLED STUDY; DOWN REGULATION; FEMALE; FLUORESCENCE MICROSCOPY; FOLLICULAR THYROID CARCINOMA; GOITER; HUMAN; HUMAN CELL; INVADOPODIUM; MAJOR CLINICAL STUDY; MALE; PAPILLARY THYROID CARCINOMA; PRIORITY JOURNAL; PROTEIN EXPRESSION; PSEUDOPODIUM; THYROID CARCINOMA; UNDIFFERENTIATED THYROID CANCER; UPREGULATION;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; CELL LINE, TUMOR; CELL MOVEMENT; CHILD; COLLAGEN; DOWN-REGULATION; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GOITER; HUMANS; MALE; MATRIX METALLOPROTEINASE 14; MATRIX METALLOPROTEINASE 2; MIDDLE AGED; NEOPLASM INVASIVENESS; PSEUDOPODIA; RELAXIN; THYROID NEOPLASMS;

EID: 79959225632     PISSN: 15417786     EISSN: 15573125     Source Type: Journal    
DOI: 10.1158/1541-7786.MCR-10-0411     Document Type: Article

References (79)

1. Silvertown JD, Summerlee AJ, Klonisch T. Relaxin-like peptides in cancer. Int J Cancer 2003;107:513-9. (Pubitemid 37296109)
2. Parry LJ, Vodstrcil LA. Relaxin physiology in the female reproductive tract during pregnancy. Adv Exp Med Biol 2007;612:34-48.
3. Ma S, Gundlach AL. Relaxin-family peptide and receptor systems in brain: insights from recent anatomical and functional studies. Adv Exp Med Biol 2007;612:119-37.
4. Conrad KP, Novak J. Emerging role of relaxin in renal and cardiovascular function. Am J Physiol Regul Integr Comp Physiol 2004;287: R250-61.
5. Klonisch T, Bialek J, Radestock Y, Hoang-Vu C, Hombach-Klonisch S. Relaxin-like ligand-receptor systems are autocrine/paracrine effectors in tumor cells and modulate cancer progression and tissue invasiveness. Adv Exp Med Biol 2007;612:104-18.
6. Nistri S, Bani D. Relaxin in vascular physiology and pathophysiology: possible implications in ischemic brain disease. Curr Neurovasc Res 2005;2:225-3.
7. Hombach-Klonisch S, Bialek J, Trojanowicz B, Weber E, Holzhausen HJ, Silvertown JD, et al. Relaxin enhances the oncogenic potential of human thyroid carcinoma cells. Am J Pathol 2006; 169:617-32. (Pubitemid 44156318)
8. Kamat AA, Feng S, Agoulnik IU, Kheradmand F, Bogatcheva NV, Coffey D, et al. The role of relaxin in endometrial cancer. Cancer Biol Ther 2006;5:71-7. (Pubitemid 43234981)
9. Thompson VC, Hurtado-Coll A, Turbin D, Fazli L, Lehman ML, Gleave ME, et al. Relaxin drives Wnt signaling through upregulation of PCDHY in prostate cancer. Prostate 2010;70:1134-45.
10. Binder C, Simon A, Binder L, Hagemann T, Schulz M, Emons G, et al. Elevated concentrations of serum relaxin are associated with meta-static disease in breast cancer patients. Breast Cancer Res Treat 2004;87:157-66. (Pubitemid 39237792)
11. Masterson R, Hewitson TD, Kelynack K, Martic M, Parry L, Bathgate R, et al. Relaxin down-regulates renal fibroblast function and promotes matrix remodelling in vitro. Nephrol Dial Transplant 2004; 19:544-52. (Pubitemid 38263111)
12. Samuel CS, Unemori EN, Mookerjee I, Bathgate RA, Layfield SL, Mak J, et al. Relaxin modulates cardiac fibroblast proliferation, differentiation, and collagen production and reverses cardiac fibrosis in vivo. Endocrinology 2004;145:4125-33. (Pubitemid 39120561)
13. Unemori EN, Pickford LB, Salles AL, Piercy CE, Grove BH, Erikson ME, et al. Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. J Clin Invest 1996;98:2739-45. (Pubitemid 26427400)
14. Williams EJ, Benyon RC, Trim N, Hadwin R, Grove BH, Arthur MJ, et al. Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo. Gut 2001; 49:577-83. (Pubitemid 32896990)
15. Unemori EN, Beck LS, Lee WP, Xu Y, Siegel M, Keller G, et al. Human relaxin decreases collagen accumulation in vivo in two rodent models of fibrosis. J Invest Dermatol 1993;101:280-5. (Pubitemid 23269897)
16. McDonald GA, Sarkar P, Rennke H, Unemori E, Kalluri R, Sukhatme VP. Relaxin increases ubiquitin-dependent degradation of fibronectin in vitro and ameliorates renal fibrosis in vivo. Am J Physiol Renal Physiol 2003;285:F59-67.
17. Samuel CS, Sakai LY, Amento EP. Relaxin regulates fibrillin 2, but not fibrillin 1, mRNA and protein expression by human dermal fibroblasts and murine fetal skin. Arch Biochem Biophys 2003;411:47-55. (Pubitemid 36268778)
18. Zhao L, Samuel CS, Tregear GW, Beck F, Wintour EM. Collagen studies in late pregnant relaxin null mice. Biol Reprod 2000;63:697-703. (Pubitemid 30659262)
19. Xu Q, Chakravorty A, Bathgate RA, Dart AM, Du XJ. Relaxin therapy reverses large artery remodeling and improves arterial compliance in senescent spontaneously hypertensive rats. Hypertension 2010;55: 1260-6.
20. Binder C, Hagemann T, Husen B, Schulz M, Einspanier A. Relaxin enhances in vitro invasiveness of breast cancer cell lines by up-regulation of matrix metalloproteases. Mol Hum Reprod 2002;8: 789-96. (Pubitemid 35012465)
21. Mookerjee I, Unemori EN, Du XJ, Tregear GW, Samuel CS. Relaxin modulates fibroblast function, collagen production, and matrix metalloproteinase- 2 expression by cardiac fibroblasts. Ann N Y Acad Sci 2005;1041:190-3. (Pubitemid 41132246)
22. McDonald JK, Schwabe C. Relaxin-induced elevations of cathepsin B and dipeptidyl peptidase I in the mouse pubic symphysis, with localization by fluorescence enzyme histochemistry. Ann N Y Acad Sci 1982;380:178-86. (Pubitemid 12128056)
23. Wang-Lee JL, Lenhart JA, Ohleth KM, Ryan PL, Bagnell CA. Regulation of urokinase- and tissue-type plasminogen activator by relaxin in the uterus and cervix of the prepubertal gilt. J Reprod Fertil 1998; 114:119-25.
24. Qin X, Garibay-Tupas J, Chua PK, Cachola L, Bryant-Greenwood GD. An autocrine/paracrine role of human decidual relaxin I. Interstitial collagenase (matrix metalloproteinase-1) and tissue plasminogen activator. Biol Reprod 1997;56:800-11.
25. Westermarck J, Kahari VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 1999;13:781-92. (Pubitemid 29220691)
26. Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010;141:52-67.
27. Herouy Y. Matrix metalloproteinases in skin pathology (Review). Int J Mol Med 2001;7:3-12.
28. Koshikawa N, Mizushima H, Minegishi T, Eguchi F, Yotsumoto F, Nabeshima K, et al. Proteolytic activation of heparin-binding EGF-like growth factor by membrane-type matrix metalloproteinase-1 in ovarian carcinoma cells. Cancer Sci 2011;102:111-6.
29. Kajita M, Itoh Y, Chiba T, Mori H, Okada A, Kinoh H, et al. Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol 2001;153:893-904. (Pubitemid 34289231)
30. Basile JR, Holmbeck K, Bugge TH, Gutkind JS. MT1-MMP controls tumor-induced angiogenesis through the release of semaphorin 4D. J Biol Chem 2007;282:6899-905. (Pubitemid 47100895)
31. Nakamura H, Ueno H, Yamashita K, Shimada T, Yamamoto E, Noguchi M, et al. Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human papillary thyroid carcinomas. Cancer Res 1999;59:467-73. (Pubitemid 29048885)
32. Zedenius J, Stahle-Backdahl M, Enberg U, Grimelius L, Larsson C, Wallin G, et al. Stromal fibroblasts adjacent to invasive thyroid tumors: expression of gelatinase A but not stromelysin 3 mRNA. World J Surg 1996;20:101-6. (Pubitemid 26006206)
33. Wasenius VM, Hemmer S, Kettunen E, Knuutila S, Franssila K, Joensuu H. Hepatocyte growth factor receptor, matrix metalloproteinase-11, tissue inhibitor of metalloproteinase-1, and fibronectin are up-regulated in papillary thyroid carcinoma: a cDNA and tissue microarray study. Clin Cancer Res 2003;9:68-75. (Pubitemid 36109717)
34. Maeta H, Ohgi S, Terada T. Protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 and 2 in papillary thyroid carcinomas. Virchows Arch 2001;438:121-8. (Pubitemid 32186579)
35. Yeh MW, Rougier JP, Park JW, Duh QY, Wong M, Werb Z, et al. Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A. Endocr Relat Cancer 2006;13:1173-83. (Pubitemid 46212571)
36. Aust G, Hofmann A, Laue S, Rost A, Kohler T, Scherbaum WA. Human thyroid carcinoma cell lines and normal thyrocytes: expression and regulation of matrix metalloproteinase-1 and tissue matrix metalloproteinase inhibitor-1 messenger-RNA and protein. Thyroid 1997;7:713-24. (Pubitemid 28086202)
37. Hofmann A, Laue S, Rost AK, Scherbaum WA, Aust G. mRNA levels of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, and MMP-9 and of their inhibitors TIMP-2 and TIMP-3 in normal thyrocytes and thyroid carcinoma cell lines. Thyroid 1998;8:203-14. (Pubitemid 28145183)
38. Henneman S, Bildt MM, Degroot J, Kuijpers-Jagtman AM, Von den Hoff JW. Relaxin stimulates MMP-2 and alpha-smooth muscle actin expression by human periodontal ligament cells. Arch Oral Biol 2008;53:161-7. (Pubitemid 350296037)
39. Kapila S, Xie Y, Wang W. Induction of MMP-1 (collagenase-1) by relaxin in fibrocartilaginous cells requires both the AP-1 and PEA-3 promoter sites. Orthod Craniofac Res 2009;12:178-86.
40. Kapila S, Xie Y. Targeted induction of collagenase and stromelysin by relaxin in unprimed and beta-estradiol-primed diarthrodial joint fibrocartilaginous cells but not in synoviocytes. Lab Invest 1998;78:925-38. (Pubitemid 28378207)
41. Qin X, Chua PK, Ohira RH, Bryant-Greenwood GD. An autocrine/paracrine role of human decidual relaxin. II. Stromelysin-1 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Biol Reprod 1997;56:812-20. (Pubitemid 27150407)
42. Lenhart JA, Ryan PL, Ohleth KM, Palmer SS, Bagnell CA. Relaxin increases secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 during uterine and cervical growth and remodeling in the pig. Endocrinology 2001;142:3941-9. (Pubitemid 32802667)
43. Lenhart JA, Ryan PL, Ohleth KM, Palmer SS, Bagnell CA. Relaxin increases secretion of tissue inhibitor of matrix metalloproteinase-1 and -2 during uterine and cervical growth and remodeling in the pig. Endocrinology 2002;143:91-8. (Pubitemid 34056407)
44. Heeg MH, Koziolek MJ, Vasko R, Schaefer L, Sharma K, Muller GA, et al. The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the Smad2 pathway. Kidney Int 2005;68:96-109. (Pubitemid 43181367)
45. Bialek J, Hombach-Klonisch S, Fiebig B, Weber E, Hoang-Vu C, Klonisch T. Lysosomal acid hydrolases of the cathepsin family are novel targets of INSL3 in human thyroid carcinoma cells. Ann N Y Acad Sci 2009;1160:361-6.
46. Ni H, Wilkins JA. Localisation of a novel adhesion blocking epitope on the human beta 1 integrin chain. Cell Adhes Commun 1998;5: 257-71. (Pubitemid 29141883)
47. Cho SY, Klemke RL. Purification of pseudopodia from polarized cells reveals redistribution and activation of Rac through assembly of a CAS/Crk scaffold. J Cell Biol 2002;156:725-36. (Pubitemid 34839887)
48. Szabova L, Son MY, Shi J, Sramko M, Yamada SS, Swaim WD, et al. Membrane-type MMPs are indispensable for placental labyrinth formation and development. Blood 2010;116:5752-61.
49. Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA, Goldberg GI. Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease. J Biol Chem 1995;270:5331-8.
50. Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 2001;17:463-516. (Pubitemid 33096184)
51. Cavalheiro BG, Junqueira CR, Brandao LG. Expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in medullary thyroid carcinoma: prognostic implications. Thyroid 2008;18:865-71.
52. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002;2:161-74. (Pubitemid 37328786)
53. Devy L, Huang L, Naa L, Yanamandra N, Pieters H, Frans N, et al. Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis. Cancer Res 2009;69:1517-26.
54. Hotary K, Allen E, Punturieri A, Yana I, Weiss SJ. Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3. J Cell Biol 2000;149:1309-23. (Pubitemid 30399683)
55. Cao J, Kozarekar P, Pavlaki M, Chiarelli C, Bahou WF, Zucker S. Distinct roles for the catalytic and hemopexin domains of membrane type 1-matrix metalloproteinase in substrate degradation and cell migration. J Biol Chem 2004;279:14129-39. (Pubitemid 38468949)
56. Li XY, Ota I, Yana I, Sabeh F, Weiss SJ. Molecular dissection of the structural machinery underlying the tissue-invasive activity of membrane type-1 matrix metalloproteinase. Mol Biol Cell 2008;19:3221-33.
57. Littlepage LE, Sternlicht MD, Rougier N, Phillips J, Gallo E, Yu Y, et al. Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression. Cancer Res 2010;70:2224-34.
58. Nakamura ES, Koizumi K, Kobayashi M, Saiki I. Inhibition of lymphangiogenesis- related properties of murine lymphatic endothelial cells and lymph node metastasis of lung cancer by the matrix metalloproteinase inhibitor MMI270. Cancer Sci 2004;95:25-31. (Pubitemid 38208403)
59. Sounni NE, Devy L, Hajitou A, Frankenne F, Munaut C, Gilles C, et al. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression. FASEB J 2002;16:555-64. (Pubitemid 34273239)
60. Holmbeck K, Bianco P, Caterina J, Yamada S, Kromer M, Kuznetsov SA, et al. MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 1999;99:81-92. (Pubitemid 29468632)
61. Ha HY, Moon HB, Nam MS, Lee JW, Ryoo ZY, Lee TH, et al. Over-expression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice. Cancer Res 2001;61:984-90.
62. Qi JH, Ebrahem Q, Moore N, Murphy G, Claesson-Welsh L, Bond M, et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med 2003;9:407-15. (Pubitemid 36460074)
63. Guo H, Li R, Zucker S, Toole BP. EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface. Cancer Res 2000;60:888-91.
64. Hombach-Klonisch S, Bialek J, Radestock Y, Truong A, Agoulnik AI, Fiebig B, et al. INSL3 has tumor-promoting activity in thyroid cancer. Int J Cancer 2010;127:521-31.
65. Klonisch T,Mustafa T, Bialek J, Radestock Y, Holzhausen HJ, Dralle H, et al. Human medullary thyroid carcinoma: a source and potential target for relaxin-like hormones. Ann N Y Acad Sci 2005;1041:449-61. (Pubitemid 41132286)
66. Plehn A, Gunther D, Aurich H, Hoang-Vu C, Weber E. Influence of proliferation, differentiation and dedifferentiation factors on the expression of the lysosomal cysteine proteinase cathepsin L (CL) in thyroid cancer cell lines. Adv Exp Med Biol 2000;477:487-95. (Pubitemid 32174034)
67. She M, Jim Yeung SC. Combining a matrix metalloproteinase inhibitor, a farnesyltransferase inhibitor, and a taxane improves survival in an anaplastic thyroid cancer model. Cancer Lett 2006;238:197-201. (Pubitemid 43867915)
68. Shi Y, Zou M. Matrix metalloproteinases in thyroid cancer. Cancer Treat Res 2004;122:179-90.
69. Radestock Y, Willing C, Kehlen A, Hoang-Vu C, Hombach-Klonisch S. Relaxin enhances S100A4 and promotes growth of human thyroid carcinoma cell xenografts. Mol Cancer Res 2010;8:494-506.
70. Silvertown JD, Ng J, Sato T, Summerlee AJ, Medin JA. H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis. Int J Cancer 2006;118:62-73. (Pubitemid 41681581)
71. Silvertown JD, Symes JC, Neschadim A, Nonaka T, Kao JC, Summerlee AJ, et al. Analog of H2 relaxin exhibits antagonistic properties and impairs prostate tumor growth. FASEB J 2007;21:754-65. (Pubitemid 46348251)
72. Feng S, Agoulnik IU, Truong A, Li Z, Creighton CJ, Kaftanovskaya EM, et al. Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis. Endocr Relat Cancer 2010;17:1021-33.
73. Silvertown JD, Geddes BJ, Summerlee AJ. Adenovirus-mediated expression of human prorelaxin promotes the invasive potential of canine mammary cancer cells. Endocrinology 2003;144:3683-91. (Pubitemid 36904448)
74. Radestock Y, Hoang-Vu C, Hombach-Klonisch S. Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells. Breast Cancer Res 2008;10:R71.
75. Tashima LS, Mazoujian G, Bryant-Greenwood GD. Human relaxins in normal, benign and neoplastic breast tissue. J Mol Endocrinol 1994;12:351-64. (Pubitemid 24199704)
76. Lamp O, Honscha KU, Jakob J, Lamp J, Schweizer S, Reischauer A, et al. Investigation of the local expression of the relaxin system in canine mammary tumours. Reprod Domest Anim 2009;44 Suppl 2:224-9.
77. Puyraimond A, Fridman R, Lemesle M, Arbeille B, Menashi S. MMP-2 colocalizes with caveolae on the surface of endothelial cells. Exp Cell Res 2001;262:28-36. (Pubitemid 32989005)
78. Nabeshima K, Inoue T, Shimao Y, Okada Y, Itoh Y, Seiki M, et al. Front-cell-specific expression of membrane-type 1 matrix metalloproteinase and gelatinase A during cohort migration of colon carcinoma cells induced by hepatocyte growth factor/scatter factor. Cancer Res 2000;60:3364-9. (Pubitemid 30482147)
79. Albiges-Rizo C, Destaing O, Fourcade B, Planus E, Block MR. Actin machinery and mechanosensitivity in invadopodia, podosomes and focal adhesions. J Cell Sci 2009;122:3037-49.