CCN3 modulates bone turnover and is a novel regulator of skeletal metastasis

Journal of Cell Communication and Signaling

Volumn 6, Issue 2, 2012, Pages 73-85

  Ouellet, Véronique ^a   Siegel, Peter M ^a,b  

^a MCGILL UNIVERSITY   (Canada)

^b MCGILL UNIVERSITY   (Canada)

Author keywords

Bone metastasis; Bone primary cancer; Breast cancer; CCN3; Osteoblast; Osteoclast

Indexed keywords

ANTINEOPLASTIC AGENT; GELATINASE A; GELATINASE B; INTERSTITIAL COLLAGENASE; MATRILYSIN; NEPHROBLASTOMA OVEREXPRESSED PROTEIN; SOMATOMEDIN BINDING PROTEIN; STROMELYSIN; THROMBOSPONDIN 1; VASCULOTROPIN;

BONE CANCER; BONE GROWTH; BONE METASTASIS; BONE TURNOVER; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CARBOXY TERMINAL SEQUENCE; CARTILAGE CELL; CELL DIFFERENTIATION; CHONDROSARCOMA; HUMAN; IN VITRO STUDY; LYMPHOCYTE TRANSFORMATION; NONHUMAN; OSTEOBLAST; PRIMARY TUMOR; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW;

EID: 84863084737     PISSN: 18739601     EISSN: 1873961X     Source Type: Journal    
DOI: 10.1007/s12079-012-0161-7     Document Type: Review

References (120)

1. Abreu JG, Ketpura NI, Reversade B, De Robertis EM (2002) Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta. Nat Cell Biol 4:599-604
2. Angelucci A, Gravina GL, Rucci N, Festuccia C, Muzi P, Vicentini C, Teti A, Bologna M (2004) Evaluation of metastatic potential in prostate carcinoma: an in vivo model. Int J Oncol 25:1713-1720
3. Arnott JA, Lambi AG, Mundy C, Hendesi H, Pixley RA, Owen TA, Safadi FF, Popoff SN (2011) The role of connective tissue growth factor (CTGF/CCN2) in skeletogenesis. Crit Rev Eukaryot Gene Expr 21:43-69
4. Athanasopoulos AN, Schneider D, Keiper T, Alt V, Pendurthi UR, Liegibel UM, Sommer U, Nawroth PP, Kasperk C, Chavakis T (2007) Vascular endothelial growth factor (VEGF)-induced up-regulation of CCN1 in osteoblasts mediates proangiogenic activities in endothelial cells and promotes fracture healing. J Biol Chem 282:26746-26753 (Pubitemid 47501957)
5. Ball DK, Rachfal AW, Kemper SA, Brigstock DR (2003) The heparin-binding 10 kDa fragment of connective tissue growth factor (CTGF) containing module 4 alone stimulates cell adhesion. J Endocrinol 176:R1-R7 (Pubitemid 36284822)
6. Benini S, Perbal B, Zambelli D, Colombo MP, Manara MC, Serra M, Parenza M, Martinez V, Picci P, Scotlandi K (2005) In Ewing's sarcoma CCN3(NOV) inhibits proliferation while promoting migration and invasion of the same cell type. Oncogene 24:4349-4361 (Pubitemid 40961758)
7. Bos PD, Zhang XH, Nadal C, Shu W, Gomis RR, Nguyen DX, Minn AJ, van de Vijver MJ, Gerald WL, Foekens JA, Massague J (2009) Genes that mediate breast cancer metastasis to the brain. Nature 459:1005-1009
8. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337-342 (Pubitemid 40852708)
9. Brigstock DR (1999) The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family. Endocr Rev 20:189-206 (Pubitemid 29339590)
10. Brigstock DR (2003) The CCN family: a new stimulus package. J Endocrinol 178:169-175 (Pubitemid 37063059)
11. Brigstock DR, Steffen CL, Kim GY, Vegunta RK, Diehl JR, Harding PA (1997) Purification and characterization of novel heparin-binding growth factors in uterine secretory fluids. Identification as heparin-regulated Mr 10,000 forms of connective tissue growth factor. J Biol Chem 272:20275-20282 (Pubitemid 27340141)
12. Brigstock DR, Goldschmeding R, Katsube KI, Lam SC, Lau LF, Lyons K, Naus C, Perbal B, Riser B, Takigawa M, Yeger H (2003) Proposal for a unified CCN nomenclature. Mol Pathol: MP 56:127-128 (Pubitemid 36461474)
13. Burren CP, Wilson EM, Hwa V, Oh Y, Rosenfeld RG (1999) Binding properties and distribution of insulin-like growth factor binding protein-related protein 3 (IGFBP-rP3/NovH), an additional member of the IGFBP Superfamily. J Clin Endocrinol Metab 84:1096-1103 (Pubitemid 29138249)
14. Canalis E (2007) Nephroblastoma overexpressed (Nov) is a novel bone morphogenetic protein antagonist. Ann N YAcad Sci 1116:50-58 (Pubitemid 350274337)
15. Canalis E (2008) Notch signaling in osteoblasts. Sci Signal 1:pe17
16. Canalis E, Smerdel-Ramoya A, Durant D, Economides AN, Beamer WG, Zanotti S (2010) Nephroblastoma overexpressed (Nov) inactivation sensitizes osteoblasts to bone morphogenetic protein-2, but nov is dispensable for skeletal homeostasis. Endocrinology 151:221-233
17. Cervello M, Giannitrapani L, Labbozzetta M, Notarbartolo M, D'Alessandro N, Lampiasi N, Azzolina A, Montalto G (2004) Expression of WISPs and of their novel alternative variants in human hepatocellular carcinoma cells. Ann N Y Acad Sci 1028:432-439 (Pubitemid 40361844)
18. Chen CC, Lau LF (2009) Functions and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol 41:771-783
19. Chevalier G, Yeger H, Martinerie C, Laurent M, Alami J, Schofield PN, Perbal B (1998) novH: differential expression in developing kidney and Wilm's tumors. Am J Pathol 152:1563-1575 (Pubitemid 28275014)
20. de Winter P, Leoni P, Abraham D (2008) Connective tissue growth factor: structure-function relationships of a mosaic, multifunctional protein. Growth Factors 26:80-91 (Pubitemid 351584060)
21. Demirpence E, Duchesne MJ, Badia E, Gagne D, Pons M (1993) MVLN cells: a bioluminescent MCE-7-derived cell line to study the modulation of estrogenic activity. J Steroid Biochem Mol Biol 46:355-364 (Pubitemid 23284493)
22. Dougall WC, Chaisson M (2006) The RANK/RANKL/OPG triad in cancer-induced bone diseases. Cancer Metastasis Rev 25:541-549 (Pubitemid 46071863)
23. Ellis PD, Chen Q, Barker PJ, Metcalfe JC, Kemp PR (2000) Nov gene encodes adhesion factor for vascular smooth muscle cells and is dynamically regulated in response to vascular injury. Arterioscler Thromb Vasc Biol 20:1912-1919 (Pubitemid 30644640)
24. Ellis PD, Metcalfe JC, Hyvonen M, Kemp PR (2003) Adhesion of endothelial cells to NOV is mediated by the integrins alphavbeta3 and alpha5beta1. J Vasc Res 40:234-243 (Pubitemid 36980725)
25. French DM, Kaul RJ, D'Souza AL, Crowley CW, Bao M, Frantz GD, Filvaroff EH, Desnoyers L (2004) WISP-1 is an osteoblastic regulator expressed during skeletal development and fracture repair. Am J Pathol 165:855-867 (Pubitemid 39129293)
26. Fu CT, Bechberger JF, Ozog MA, Perbal B, Naus CC (2004) CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible mechanism of connexin-mediated growth suppression. J Biol Chem 279:36943-36950 (Pubitemid 39129044)
27. Gao R, Brigstock DR (2003) Low density lipoprotein receptor-related protein (LRP) is a heparin-dependent adhesion receptor for connective tissue growth factor (CTGF) in rat activated hepatic stellate cells. Hepatol Res Offic J Jpn Soc Hepatol 27:214-220 (Pubitemid 37407669)
28. Garcia Abreu J, Coffinier C, Larrain J, Oelgeschlager M, De Robertis EM (2002) Chordin-like CR domains and the regulation of evolutionarily conserved extracellular signaling systems. Gene 287:39-47 (Pubitemid 34454797)
29. Gazzerro E, Canalis E (2006) Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord 7:51-65 (Pubitemid 46044349)
30. Ghayad SE, Vendrell JA, Bieche I, Spyratos F, Dumontet C, Treilleux I, Lidereau R, Cohen PA (2009) Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer. J Mol Endocrinol 42:87-103
31. Girdler F, Brotherick I (2000) The oestrogen receptors (ER alpha and ER beta) and their role in breast cancer: a review. Breast 9:194-200
32. Gori F, Hofbauer LC, Dunstan CR, Spelsberg TC, Khosla S, Riggs BL (2000) The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromal-osteoblast lineage cells is developmentally regulated. Endocrinology 141:4768-4776 (Pubitemid 32055158)
33. Guillon-Munos A, Oikonomopoulou K, Michel N, Smith CR, Petit-Courty A, Canepa S, Reverdiau P, Heuze-Vourc'h N, Diamandis EP, Courty Y (2011) Kallikrein-related peptidase 12 hydrolyzes matricellular proteins of the CCN family and modifies interactions of CCN1 and CCN5 with growth factors. J Biol Chem 286:25505-25518
34. Hadjiargyrou M, Lombardo F, Zhao S, Ahrens W, Joo J, Ahn H, Jurman M, White DW, Rubin CT (2002) Transcriptional profiling of bone regeneration. Insight into the molecular complexity of wound repair. J Biol Chem 277:30177-30182
35. Hashimoto G, Inoki I, Fujii Y, Aoki T, Ikeda E, Okada Y (2002) Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165. J Biol Chem 277:36288-36295
36. Heath E, Tahri D, Andermarcher E, Schofield P, Fleming S, Boulter CA (2008) Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the Nov (Ccn3) gene. BMC Dev Biol 8:18
37. Hirschfeld M, zur Hausen A, Bettendorf H, Jager M, Stickeler E (2009) Alternative splicing of Cyr61 is regulated by hypoxia and significantly changed in breast cancer. Cancer Res 69:2082-2090
38. Holbourn KP, Perbal B, Ravi Acharya K (2009) Proteins on the catwalk: modelling the structural domains of the CCN family of proteins. J Cell Commun Signal 3:25-41
39. Huang CY, Lee CY, Chen MY, Tsai HC, Hsu HC, Tang CH (2011) Nephroblastoma overexpressed gene (NOV) enhances cell motility and COX-2 upregulation of human osteosarcoma involves alphavbeta5 integrin, ILK and AP-1-dependent pathways. Biochem Pharmacol 81:577-585
40. Inoki I, Shiomi T, Hashimoto G, Enomoto H, Nakamura H, Makino K, Ikeda E, Takata S, Kobayashi K, Okada Y (2002) Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis. FASEB J Off Publ Fed Am Soc Exp Biol 16:219-221
41. Jamil N, Howie S, Salter DM (2010) Therapeutic molecular targets in human chondrosarcoma. Int J Exp Pathol 91:387-393
42. Jiang WG, Watkins G, Fodstad O, Douglas-Jones A, Mokbel K, Mansel RE (2004) Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer. Endocr-Relat Cancer 11:781-791 (Pubitemid 40065551)
43. Joliot V, Martinerie C, Dambrine G, Plassiart G, Brisac M, Crochet J, Perbal B (1992) Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas. Mol Cell Biol 12:10-21
44. Jurgens H, Dirksen U (2011) Ewing sarcoma treatment. Eur J Cancer 47(Suppl 3):S366-S367
45. Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA, Massague J (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537-549 (Pubitemid 36808649)
46. Katsube K, Ichikawa S, Katsuki Y, Kihara T, Terai M, Lau LF, Tamamura Y, Takeda S, Umezawa A, Sakamoto K, Yamaguchi A (2009a) CCN3 and bone marrow cells. J Cell Commun Signal 3:135-145
47. Katsube K, Sakamoto K, Tamamura Y, Yamaguchi A (2009b) Role of CCN, a vertebrate specific gene family, in development. Develop Growth Differ 51:55-67
48. Katsuki Y, Sakamoto K, Minamizato T, Makino H, Umezawa A, Ikeda MA, Perbal B, Amagasa T, Yamaguchi A, Katsube K (2008) Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1. Biochem Biophys Res Commun 368:808-814
49. Kawai J, Akiyama H, Shigeno C, Ito H, Konishi J, Nakamura T (1999) Effects of transforming growth factor-beta signaling on chondrogenesis in mouse chondrogenic EC cells, ATDC5. Eur J Cell Biol 78:707-714 (Pubitemid 29505057)
50. Kawaki H, Kubota S, Suzuki A, Lazar N, Yamada T, Matsumura T, Ohgawara T, Maeda T, Perbal B, Lyons KM, Takigawa M (2008) Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 shown by a comprehensive analysis of the CCN family proteins in cartilage. J Bone Miner Res Off J Am Soc Bone Miner Res 23:1751-1764
51. Khosla S (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology 142:5050-5055 (Pubitemid 33131929)
52. Kim HS, Nagalla SR, Oh Y, Wilson E, Roberts CT Jr, Rosenfeld RG (1997) Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): characterization of connective tissue growth factor as a member of the IGFBP superfamily. Proc Natl Acad Sci U S A 94:12981-12986 (Pubitemid 27518462)
53. Kireeva ML, Latinkic BV, Kolesnikova TV, Chen CC, Yang GP, Abler AS, Lau LF (1997) Cyr61 and Fisp12 are both ECM-associated signaling molecules: activities, metabolism, and localization during development. Exp Cell Res 233:63-77 (Pubitemid 27229982)
54. Krishnan V, Bryant HU, Macdougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202-1209
55. Kular L, Pakradouni J, Kitabgi P, Laurent M, Martinerie C (2011) The CCN family: a new class of inflammation modulators? Biochimie 93:377-388
56. Kyurkchiev S, Yeger H, Bleau AM, Perbal B (2004) Potential cellular conformations of the CCN3(NOV) protein. Cell Commun Signal: CCS 2:9
57. Lazar N, Manara C, Navarro S, Bleau AM, Llombart-Bosch A, Scotlandi K, Planque N, Perbal B (2007) Domain-specific CCN3 antibodies as unique tools for structural and functional studies. J Cell Commun Signal 1:91-102
58. Leask A, Abraham DJ (2006) All in the CCN family: essential matricellular signaling modulators emerge from the bunker. J Cell Sci 119:4803-4810 (Pubitemid 46017793)
59. Leng E, Malcolm T, Tai G, Estable M, Sadowski I (2002) Organization and expression of the Cyr61 gene in normal human fibroblasts. J Biomed Sci 9:59-67 (Pubitemid 34124208)
60. Lin CG, Chen CC, Leu SJ, Grzeszkiewicz TM, Lau LF (2005) Integrin-dependent functions of the angiogenic inducer NOV (CCN3): implication in wound healing. J Biol Chem 280:8229-8237 (Pubitemid 40349724)
61. Long F (2011) Building strong bones: molecular regulation of the osteoblast lineage. Nature reviews. Mol Cell Biol 13:27-38
62. Mahony D, Kalionis B, Antalis TM (1999) Plasminogen activator inhibitor type-2 (PAI-2) gene transcription requires a novel NF-kappaB-like transcriptional regulatory motif. Eur J Biochem/FEBS 263:765-772 (Pubitemid 29361949)
63. Maillard M, Cadot B, Ball RY, Sethia K, Edwards DR, Perbal B, Tatoud R (2001) Differential expression of the ccn3 (nov) protooncogene in human prostate cell lines and tissues. Mol Pathol: MP 54:275-280 (Pubitemid 32730406)
64. Manara MC, Perbal B, Benini S, Strammiello R, Cerisano V, Perdichizzi S, Serra M, Astolfi A, Bertoni F, Alami J, Yeger H, Picci P, Scotlandi K (2002) The expression of ccn3(nov) gene in musculoskeletal tumors. Am J Pathol 160:849-859 (Pubitemid 34224575)
65. Marie PJ (2008) Transcription factors controlling osteoblastogenesis. Arch Biochem Biophys 473:98-105
66. Martinerie C, Viegas-Pequignot E, Nguyen VC, Perbal B (1997) Chromosomal mapping and expression of the human cyr61 gene in tumour cells from the nervous system. Mol Pathol: MP 50:310-316 (Pubitemid 28057241)
67. McCallum L, Irvine AE (2009) CCN3 - a key regulator of the hematopoietic compartment. Blood Rev 23:79-85
68. McCallum L, Price S, Planque N, Perbal B, Pierce A, Whetton AD, Irvine AE (2006) A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation. Blood 108:1716-1723 (Pubitemid 44316142)
69. Minamizato T, Sakamoto K, Liu T, Kokubo H, Katsube K, Perbal B, Nakamura S, Yamaguchi A (2007) CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways. Biochem Biophys Res Commun 354:567-573 (Pubitemid 46161361)
70. Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massague J (2005) Genes that mediate breast cancer metastasis to lung. Nature 436:518-524 (Pubitemid 41112921)
71. Nakata E, Nakanishi T, Kawai A, Asaumi K, Yamaai T, Asano M, Nishida T, Mitani S, Inoue H, Takigawa M (2002) Expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) during fracture healing. Bone 31:441-447 (Pubitemid 35175446)
72. Negishi-Koga T, Takayanagi H (2009) Ca2 + -NFATc1 signaling is an essential axis of osteoclast differentiation. Immunol Rev 231:241-256
73. Ohgawara T, Kubota S, Kawaki H, Kurio N, Abd El Kader T, Hoshijima M, Janune D, Shimo T, Perbal B, Sasaki A, Takigawa M (2011) Association of the metastatic phenotype with CCN family members among breast and oral cancer cells. J Cell Commun Signal
74. Ooi LL, Zheng Y, Stalgis-Bilinski K, Dunstan CR (2011) The bone remodeling environment is a factor in breast cancer bone metastasis. Bone 48:66-70
75. Ouellet V, Tiedemann K, Mourskaia A, Fong JE, Tran-Thanh D, Amir E, Clemons M, Perbal B, Komarova SV, Siegel PM (2011) CCN3 impairs osteoblast and stimulates osteoclast differentiation to favor breast cancer metastasis to bone. Am J Pathol 178:2377-2388
76. Parisi MS, Gazzerro E, Rydziel S, Canalis E (2006) Expression and regulation of CCN genes in murine osteoblasts. Bone 38:671-677
77. Payet LD, Wang XH, Baxter RC, Firth SM (2003) Amino- and carboxyl-terminal fragments of insulin-like growth factor (IGF) binding protein-3 cooperate to bind IGFs with high affinity and inhibit IGF receptor interactions. Endocrinology 144:2797-2806 (Pubitemid 36819879)
78. Pennica D, Swanson TA, Welsh JW, Roy MA, Lawrence DA, Lee J, Brush J, Taneyhill LA, Deuel B, Lew M, Watanabe C, Cohen RL, Melhem MF, Finley GG, Quirke P, Goddard AD, Hillan KJ, Gurney AL, Botstein D, Levine AJ (1998) WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors. Proc Natl Acad Sci U S A 95:14717-14722 (Pubitemid 29003696)
79. Perbal B (1999) Nuclear localisation of NOVH protein: a potential role for NOV in the regulation of gene expression. Mol Pathol: MP 52:84-91 (Pubitemid 29166730)
80. Perbal B (2001) NOV (nephroblastoma overexpressed) and the CCN family of genes: structural and functional issues. Mol Pathol: MP 54:57-79 (Pubitemid 32269998)
81. Perbal B (2006) NOV story: the way to CCN3. Cell Commun Signal: CCS 4:3
82. Perbal B (2009) Alternative splicing of CCN mRNAs⋯. it has been upon us. J Cell Commun Signal 3:153-157
83. Perbal B, Takigawa M (2005) CCN proteins: a new family of cell growth and differentiation regulators. Imprerial College Press
84. Perbal B, Martinerie C, Sainson R, Werner M, He B, Roizman B (1999) The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling. Proc Natl Acad Sci U S A 96:869-874
85. Perbal B, Zuntini M, Zambelli D, Serra M, Sciandra M, Cantiani L, Lucarelli E, Picci P, Scotlandi K (2008) Prognostic value of CCN3 in osteosarcoma. Clin Cancer Res Off J Am Assoc Cancer Res 14:701-709 (Pubitemid 351231150)
86. Perbal B, Lazar N, Zambelli D, Lopez-Guerrero JA, Llombart-Bosch A, Scotlandi K, Picci P (2009) Prognostic relevance of CCN3 in Ewing sarcoma. Hum Pathol 40:1479-1486
87. Planque N, Long Li C, Saule S, Bleau AM, Perbal B (2006) Nuclear addressing provides a clue for the transforming activity of aminotruncated CCN3 proteins. J Cell Biochem 99:105-116 (Pubitemid 44297954)
88. Rose AA, Pepin F, Russo C, Abou Khalil JE, Hallett M, Siegel PM (2007) Osteoactivin promotes breast cancer metastasis to bone. Mol Cancer Res: MCR 5:1001-1014 (Pubitemid 350070756)
89. Rydziel S, Stadmeyer L, Zanotti S, Durant D, Smerdel-Ramoya A, Canalis E (2007) Nephroblastoma overexpressed (Nov) inhibits osteoblastogenesis and causes osteopenia. J Biol Chem 282:19762-19772 (Pubitemid 47100103)
90. Sakamoto K, Yamaguchi S, Ando R, Miyawaki A, Kabasawa Y, Takagi M, Li CL, Perbal B, Katsube K (2002) The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway. J Biol Chem 277:29399-29405 (Pubitemid 41079223)
91. Sanceau J, Truchet S, Bauvois B (2003) Matrix metalloproteinase-9 silencing by RNA interference triggers the migratory-adhesive switch in Ewing's sarcoma cells. J Biol Chem 278:36537-36546 (Pubitemid 37139984)
92. Schutze N, Noth U, Schneidereit J, Hendrich C, Jakob F (2005) Differential expression of CCN-family members in primary human bone marrow-derived mesenchymal stem cells during osteogenic, chondrogenic and adipogenic differentiation. Cell Commun Signal: CCS 3:5
93. Shimoyama T, Hiraoka S, Takemoto M, Koshizaka M, Tokuyama H, Tokuyama T, Watanabe A, Fujimoto M, Kawamura H, Sato S, Tsurutani Y, Saito Y, Perbal B, Koseki H, Yokote K (2010) CCN3 inhibits neointimal hyperplasia through modulation of smooth muscle cell growth and migration. Arterioscler Thromb Vasc Biol 30:675-682
94. Sin WC, Tse M, Planque N, Perbal B, Lampe PD, Naus CC (2009) Matricellular protein CCN3 (NOV) regulates actin cytoskeleton reorganization. J Biol Chem 284:29935-29944
95. Smerdel-Ramoya A, Zanotti S, Canalis E (2011) Nephroblastoma overexpressed (Nov) induces gremlin in ST-2 stromal cell lines by post-transcriptional mechanisms. J Cell Biochem 112:715-722
96. Su BY, Cai WQ, Zhang CG, Martinez V, Lombet A, Perbal B (2001) The expression of ccn3 (nov) RNA and protein in the rat central nervous system is developmentally regulated. Mol Pathol: MP 54:184-191 (Pubitemid 32539612)
97. Su JL, Chiou J, Tang CH, Zhao M, Tsai CH, Chen PS, Chang YW, Chien MH, Peng CY, Hsiao M, Kuo ML, Yen ML (2010) CYR61 regulates BMP-2-dependent osteoblast differentiation through the {alpha}v{beta}3 integrin/integrin-linked kinase/ERK pathway. J Biol Chem 285:31325-31336
98. Subramaniam MM, Lazar N, Navarro S, Perbal B, Llombart-Bosch A (2008) Expression of CCN3 protein in human Wilms' tumors: immunohistochemical detection of CCN3 variants using domain-specific antibodies. Virchows Arch Int J Pathol 452:33-39
99. Tabaries S, Dong Z, Annis MG, Omeroglu A, Pepin F, Ouellet V, Russo C, Hassanain M, Metrakos P, Diaz Z, Basik M, Bertos N, Park M, Guettier C, Adam R, Hallett M, Siegel PM (2011) Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes. Oncogene 30:1318-1328
100. Tan TW, Huang YL, Chang JT, Lin JJ, Fong YC, Kuo CC, Tsai CH, Chen YJ, Hsu HC, Cho DY, Chen YH, Tang CH (2011) CCN3 increases BMP-4 expression and bone mineralization in osteoblasts. J Cell Physiol
101. Tanaka S, Sugimachi K, Saeki H, Kinoshita J, Ohga T, Shimada M, Maehara Y (2001) A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma. Oncogene 20:5525-5532 (Pubitemid 32889489)
102. Tanaka S, Sugimachi K, Kameyama T, Maehara S, Shirabe K, Shimada M, Wands JR, Maehara Y (2003) Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma. Hepatology 37:1122-1129 (Pubitemid 36538689)
103. Tang N, Song WX, Luo J, Haydon RC, He TC (2008) Osteosarcoma development and stem cell differentiation. Clin Orthop Relat Res 466:2114-2130
104. Thomas DM, Johnson SA, Sims NA, Trivett MK, Slavin JL, Rubin BP, Waring P, McArthur GA, Walkley CR, Holloway AJ, Diyagama D, Grim JE, Clurman BE, Bowtell DD, Lee JS, Gutierrez GM, Piscopo DM, Carty SA, Hinds PW (2004) Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma. J Cell Biol 167:925-934 (Pubitemid 39628114)
105. Thomopoulos GN, Kyurkchiev S, Perbal B (2001) Immunocytochemical localization of NOVH protein and ultrastructural characteristics of NCI-H295R cells. J Submicrosc Cytol Pathol 33:251-260 (Pubitemid 33760000)
106. Tong ZY, Brigstock DR (2006) Intrinsic biological activity of the thrombospondin structural homology repeat in connective tissue growth factor. J Endocrinol 188:R1-R8
107. Tzeng HE, Chen JC, Tsai CH, Kuo CC, Hsu HC, Hwang WL, Fong YC, Tang CH (2011) CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma through integrin dependent pathway. J Cell Physiol
108. Valcourt U, Gouttenoire J, Aubert-Foucher E, Herbage D, Mallein-Gerin F (2003) Alternative splicing of type II procollagen pre-mRNA in chondrocytes is oppositely regulated by BMP-2 and TGF-beta1. FEBS Lett 545:115-119 (Pubitemid 36694686)
109. Vallacchi V, Rodolfo M (2009) Regulatory role of CCN3 in melanoma cell interaction with the extracellular matrix. Cell Adhes Migr 3:7-10
110. Vendrell JA, Magnino F, Danis E, Duchesne MJ, Pinloche S, Pons M, Birnbaum D, Nguyen C, Theillet C, Cohen PA (2004) Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol 32:397-414 (Pubitemid 38584644)
111. Voorberg J, Fontijn R, Calafat J, Janssen H, van Mourik JA, Pannekoek H (1991) Assembly and routing of von Willebrand factor variants: the requirements for disulfide-linked dimerization reside within the carboxy-terminal 151 amino acids. J Cell Biol 113:195-205 (Pubitemid 21909686)
112. Vorwerk P, Hohmann B, Oh Y, Rosenfeld RG, Shymko RM (2002) Binding properties of insulin-like growth factor binding protein-3 (IGFBP-3), IGFBP-3N- and C-terminal fragments, and structurally related proteins mac25 and connective tissue growth factor measured using a biosensor. Endocrinology 143:1677-1685 (Pubitemid 34415882)
113. Xie D, Nakachi K, Wang H, Elashoff R, Koeffler HP (2001) Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features. Cancer Res 61:8917-8923 (Pubitemid 34013909)
114. Yamaguchi A, Sakamoto K, Minamizato T, Kenichi K, Soichi N (2008) Regulation of osteoblast differentiation mediated by BMP, Notch, and CCN3/NOV. Jpn Dent Sci Rev 44:48-56
115. Yan X, Baxter RC, Perbal B, Firth SM (2006) The aminoterminal insulin-like growth factor (IGF) binding domain of IGF binding protein-3 cannot be functionally substituted by the structurally homologous domain of CCN3. Endocrinology 147:5268-5274 (Pubitemid 44790582)
116. Yanagita T, Kubota S, Kawaki H, Kawata K, Kondo S, Takano-Yamamoto T, Tanaka S, Takigawa M (2007) Expression and physiological role of CCN4/Wnt-induced secreted protein 1 mRNA splicing variants in chondrocytes. FEBS J 274:1655-1665 (Pubitemid 46426900)
117. Yu C, Le AT, Yeger H, Perbal B, Alman BA (2003) NOV (CCN3) regulation in the growth plate and CCN family member expression in cartilage neoplasia. J Pathol 201:609-615 (Pubitemid 38256411)
118. Zhang R, Averboukh L, Zhu W, Zhang H, Jo H, Dempsey PJ, Coffey RJ, Pardee AB, Liang P (1998) Identification of rCop-1, a new member of the CCN protein family, as a negative regulator for cell transformation. Mol Cell Biol 18:6131-6141 (Pubitemid 28450564)
119. Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, Foekens JA, Massague J (2009) Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 16:67-78
120. Zuo GW, Kohls CD, He BC, Chen L, Zhang W, Shi Q, Zhang BQ, Kang Q, Luo J, Luo X, Wagner ER, Kim SH, Restegar F, Haydon RC, Deng ZL, Luu HH, He TC, Luo Q (2010) The CCN proteins: important signaling mediators in stem cell differentiation and tumorigenesis. Histol Histopathol 25:795-806