BMP9 inhibits the bone metastasis of breast cancer cells by downregulating CCN2 (connective tissue growth factor, CTGF) expression

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• 作者：Wei Ren (1)
  Xiaoxiao Sun (2)
  Ke Wang (2)
  Honglei Feng (2)
  Yuehong Liu (2)
  Chang Fei (2)
  Shaoheng Wan (2)
  Wei Wang (2)
  Jinyong Luo (2)
  Qiong Shi (2)
  Min Tang (2)
  Guowei Zuo (2)
  Yaguang Weng (2)
  Tongchuan He (3)
  Yan Zhang (2)
  
• 关键词：BMP9 ; Breast cancer ; Bone metastasis ; CTGF
• 刊名：Molecular Biology Reports
• 出版年：2014
• 出版时间：March 2014
• 年：2014
• 卷：41
• 期：3
• 页码：1373-1383
• 全文大小：5,318 KB
• 参考文献：1. Akiyoshi T, Uchida K, Tateyama S (2004) Expression of bone morphogenetic protein-6 (BMP-6) and BMP receptors in myoepithelial cells of canine mammary gland tumors. Vet Pathol 41:154-63 CrossRef
  2. Miksits M, Wlcek K, Svoboda M, Thalhammer T, Ellinger I, Stefanzl G, Falany CN, Szekeres T, Jaeger W (2011) The anti-progestin RU-486 inhibits viability of MCF-7 breast cancer cells by suppressing WNT1. Cancer Lett 312:101-08 CrossRef
  3. Ye L, Kynaston H, Jiang WG (2008) Bone morphogenetic protein-9 induces apoptosis in prostate cancer cells, the role of prostate apoptosis response-4. Mol Cancer Res 6:1594-606 CrossRef
  4. Miyazono K, Maeda S, Imamura T (2005) BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16:251-63 CrossRef
  5. Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425:577-84 CrossRef
  6. Ye L, Lewis-Russell JM, Kyanaston HG, Jiang WG (2007) Bone morphogenetic proteins and their receptor signaling in prostate cancer. Histol Histopathol 22:1129-147
  7. Alarmo EL, Korhonen T, Kuukasj?rvi T, Huhtala H, Holli K, Kallioniemi A (2008) Bone morphogenetic protein 7 expression associates with bone metastasis in breast carcinomas. Ann Oncol 19:19308-9314 CrossRef
  8. Alarmo EL, P?rssinen J, Ketolainen JM, Savinainen K, Karhu R, Kallioniemi A (2009) BMP7 influences proliferation, migration, and invasion of breast cancer cells. Cancer Lett 275:35-3 CrossRef
  9. Buijs JT, Henriquez NV, van Overveld PG, van der Horst G, Que I, Schwaninger R, Rentsch C, Ten Dijke P, Cleton-Jansen AM, Driouch K, Lidereau R, Bachelier R, Vukicevic S, Clézardin P, Papapoulos SE, Cecchini MG, L?wik CW, van der Pluijm G (2007) Bone morphogenetic protein 7 in the development and treatment of bone metastases from breast cancer. Cancer Res 67:8742-751 CrossRef
  10. Katsuno Y, Hanyu A, Kanda H, Ishikawa Y, Akiyama F, Iwase T, Ogata E, Ehata S, Miyazono K, Imamura T (2008) Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway. Oncogene 27:6322-333 CrossRef
  11. Lin YE, Bokobza Sivan M, Jiang WenG (2009) Bone morphogenetic proteins in development and progression of breast cancer and therapeutic potential. Int J Mol Med 24:591-97
  12. Wang L, Ling Y, Chen Y, Li CL, Feng F, You QD, Lu N, Guo QL (2011) Flavonoid baicalein suppresses adhesion, migration and invasion of MDA-MB-231 human breast cancer cells. Cancer Lett 297:42-8 CrossRef
  13. Wang K, Feng H, Ren W, Sun X, Luo J, Tang M, Zhou L, Weng Y, He TC, Zhang Y (2011) BMP9 inhibits the proliferation and invasiveness of breast cancer cells MDA-MB-231. J Cancer Res Clin Oncol 137:1687-696 CrossRef
  14. Deng H, Makizumi R, Ravikumar TS, Dong H, Yang W, Yang WL (2007) Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells. Exp Cell Res 313:1033-044 CrossRef
  15. Gordon KJ, Kirkbride KC, How T, Blobe GC (2009) Bone morphogenetic proteins induce pancreatic cancer cell invasiveness through a Smad1-dependent mechanism that involves matrix metalloproteinase-2. Carcinogenesis 30:238-48 CrossRef
  16. Kim JH, Kim KY, Jeon JH, Lee SH, Hwang JE, Lee JH, Kim KK, Lim JS, Kim KI, Moon EY, Lee HG, Ryu JH, Yang Y (2008) Adipocyte culture medium stimulates production of macrophage inhibitory cytokine 1 in MDA-MB-231 cells. Cancer Lett 261:253-62 CrossRef
  17. Thériault BL, Shepherd TG, Mujoomdar ML, Nachtigal MW (2007) BMP4 induces EMT and Rho GTPase activation in human ovarian cancer cells. Carcinogenesis 28:1153-162 CrossRef
  18. Chen C, Grzegorzewski KJ, Barash S, Zhao Q, Schneider H, Wang Q, Singh M, Pukac L, Bell AC, Duan R, Coleman T, Duttaroy A, Cheng S, Hirsch J, Zhang L, Lazard Y, Fischer C, Barber MC, Ma ZD, Zhang YQ, Reavey P, Zhong L, Teng B, Sanyal I, Ruben SM, Blondel O, Birse CE (2003) An integrated functional genomics screening program reveals a role for BMP-9in glucose homeostasis. Nat Biotechnol 21:294-01 CrossRef
  19. David L, Mallet C, Mazerbourg S, Feige JJ, Bailly S (2007) Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood 109:1953-961 CrossRef
  20. Helm GA, Alden TD, Beres EJ, Hudson SB, Das S, Engh JA, Pittman DD, Kerns KM, Kallmes DF (2000) Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent. J Neurosurg 92:191-96
  21. Lopez-Coviella I, Berse B, Krauss R, Thies RS, Blusztajn JK (2000) Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9. Science 289:313-16 CrossRef
  22. Ploemacher RE, Engels LJ, Mayer AE, Thies S, Neben S (1999) Bone morphogenetic protein 9 is a potent synergistic factor for murine hemopoietic progenitor cell generation and colony formation in serum-free cultures. Leukemia 13:428-37 CrossRef
  23. Truksa J, Peng H, Lee P, Beutler E (2006) Bone morphogenetic proteins 2, 4, and 9st imulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci USA 103:10289-0293 CrossRef
  24. Lee Y, Schwarz E, Davies M, Jo M, Gates J, Wu J, Zhang X, Lieberman JR (2003) Differences in the cytokine profiles associated with prostate cancer cell induced osteoblastic and osteolytic lesions in bone. J Orthop Res 21:62-2 CrossRef
  25. Herrera B, van Dinther M, Ten Dijke P, Inman GJ (2009) Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer cell proliferation. Cancer Res 69:9254-262 CrossRef
  26. Scharpfenecker M, van Dinther M, Liu Z, van Bezooijen RL, Zhao Q, Pukac L, L?wik CW, ten Dijke P (2007) BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis. J Cell Sci 120:964-72 CrossRef
  27. Varady P, Li JZ, Cunningham M, Beres EJ, Das S, Engh J, Alden TD, Pittman DD, Kerns KM, Kallmes DF, Helm GA (2001) Morphologic analysis of BMP-9 gene therapy-induced osteogenesis. Hum Gene Ther 12:697-10 CrossRef
  28. Bergeron E, Marquis ME, Chretien I, Faucheux N (2007) Differentiation of preosteoblasts using a delivery system with BMPs and bioactive glass microspheres. J Mater Sci Mater Med 18:255-63 CrossRef
  29. Song JJ, Celeste AJ, Kong FM, Jirtle RL, Rosen V, Thies RS (1995) Bone morphogenetic protein-9 binds to liver cells and stimulates proliferation. Endocrinology 136:4293-297
  30. Lu X, Kang Y (2009) Efficient acquisition of dual metastasis organotropism to bone and lung through stable spontaneous fusion between MDA-MB-231 variants. Proc Natl Acad Sci USA 106:9385-390 CrossRef
  31. Chien W, O’Kelly J, Lu D, Leiter A, Sohn J, Yin D, Karlan B, Vadgama J, Lyons KM, Koeffler HP (2011) Expression of connective tissue growth factor (CTGF/CTGF) in breast cancer cells is associated with increased migration and angiogenesis. Int J Oncol 38:1741-747
  32. Igarashi A, Nashiro K, Kikuchi K, Sato S, Ihn H, Grotendorst GR, Takehara K (1995) Significant correlation between connective tissue growth factor gene expression and skin sclerosis in tissue sections from patients with systemic sclerosis. J Invest Dermatol 105:280-84 CrossRef
  33. Oemar BS, Werner A, Garnier JM, Do DD, Godoy N, Nauck M, M?rz W, Rupp J, Pech M, Lüscher TF (1997) Human connective tissue growth factor is expressed in advanced atherosclerotic lesions. Circulation 95:831-39 CrossRef
  34. Du J, Yang S, Wang Z, Zhai C, Yuan W, Lei R, Zhang J, Zhu T (2008) Bone morphogenetic protein 6 inhibit stress-induced breast cancer cells apoptosis via both Smad and p38 pathways. J Cell Biochem 103:1584-597 CrossRef
  35. Hamada S, Satoh K, Hirota M, Kimura K, Kanno A, Masamune A, Shimosegawa T (2007) Bone morphogenetic protein 4 induces epithelialmesenchymal transition through MSX2 induction on pancreatic cancer cell line. J Cell Physiol 213:768-74 CrossRef
  36. Tamatani T, Kobayashi H, Tezuka K, Sakamoto S, Suzuki K, Nakanishi T, Takigawa M, Miyano T (1998) Establishment of the enzyme-linked immunosorbent assay for connective tissue growth factor (CTGF) and its detection in the sera of biliary atresia. Biochem Biophys Res Commun 251:748-52 CrossRef
  37. Yang S, Zhong C, Frenkel B, Reddi AH, Roy-Burman P (2005) Diverse biological effect and Smad signaling of bone morphogenetic protein 7 in prostate tumor cells. Cancer Res 65:5769-777 CrossRef
  
• 作者单位：Wei Ren (1)
  Xiaoxiao Sun (2)
  Ke Wang (2)
  Honglei Feng (2)
  Yuehong Liu (2)
  Chang Fei (2)
  Shaoheng Wan (2)
  Wei Wang (2)
  Jinyong Luo (2)
  Qiong Shi (2)
  Min Tang (2)
  Guowei Zuo (2)
  Yaguang Weng (2)
  Tongchuan He (3)
  Yan Zhang (2)
  
  1. Department of General Surgery, The First Affiliated Hospitals of Chongqing Medical University, Chongqing, 400016, China
  2. Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, 1 YiXueYuan Road, Yuzhong District, Chongqing, 400016, China
  3. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL, USA
  
• ISSN：1573-4978

文摘

Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration, and apoptosis. BMP9, the latest BMP to be discovered, is reportedly expressed in a variety of human carcinoma cell lines, but the role of BMP9 in breast cancer has not been fully clarified. In a previous study, BMP9 was found to inhibit the growth, migration, and invasiveness of MDA-MB-231 breast cancer cells. In the current study, the effect of BMP9 on the bone metastasis of breast cancer cells was investigated. After absent or low expression of BMP9 was detected in the MDA-MB-231 breast cancer cells and breast non-tumor adjacent tissues using Western blot and immunohistochemistry, In our previous study, BMP9 could inhibit the proliferation and invasiveness of breast cancer cells MDA-MB-231 in vitro and in vivo. This paper shows that BMP9 inhibit the bone metastasis of breast cancer cells by activating the BMP/Smad signaling pathway and downregulating connective tissue growth factor (CTGF); however, when CTGF expression was maintained, the inhibitory effect of BMP9 on the MDA-MB-231 cells was abolished. Together, these observations indicate that BMP9 is an important mediator of breast cancer bone metastasis and a potential therapeutic target for treating this deadly disease.