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Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells

  • Authors:
    • Bo Liu
    • Jian Cui
    • Jing Sun
    • Juan Li
    • Xiuchun Han
    • Jie Guo
    • Min Yi
    • Norio Amizuka
    • Xin Xu
    • Minqi Li
  • View Affiliations / Copyright

    Affiliations: Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China, Department of Advanced Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaidō 060‑8638, Japan, Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Hokkaidō 060‑8586, Japan
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1099-1106
    |
    Published online on: June 7, 2016
       https://doi.org/10.3892/mmr.2016.5374
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Abstract

The aim of the present study was to investigate the expression of matrix metalloproteinase (MMP)9 and MMP2, and their potential roles in bone metastasis nests using a well-standardized model of breast cancer bone metastasis in nude mice. BALB/c nu/nu mice (5-week-old; n=10) were subjected to intracardiac injection of MDA-MB-231 human breast cancer cells. After 4 weeks, the mice exhibiting radiolucent lesions in tibiae were sacrificed, and the tibiae were removed for histochemical analysis. The gene expression of MMP2 and MMP9 in the tumor cells, metaphysis and diaphysis of normal BALB/c nu/nu mice were determined using reverse transcription-polymerase chain reaction analysis. The metastatic tumor tissue occupied almost the entire bone marrow cavity. Numerous tartrate-resistant acid phosphatase-positive osteoclasts were found in the metastasized lesions. The invaded tumor cells positive for mammaglobin 1 exhibited different proliferation activities and apoptosis between the metaphysis and diaphysis. Proliferating cell nuclear antigen was expressed at high levels in the metaphyseal area, whereas TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells were more evident in the diaphysis area. Of note, MMP9 was expressed predominantly in the proliferating cell nuclear antigen‑positive area, whereas the expression of MMP2 was observed predominantly in the diaphysis, which had more TUNEL‑positive cells. Taken together, the results suggested that MMP9 and MMP2 may have their own importance in extracellular matrix degradation and trabecular bone damage in different zones of bone metastasis, including the metaphysis and diaphysis.
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1 

Coleman RE: Metastatic bone disease: Clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 27:165–176. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Hamaoka T, Madewell JE, Podoloff DA, Hortobagyi GN and Ueno NT: Bone imaging in metastatic breast cancer. J Clin Oncol. 22:2942–2953. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Kozlow W and Guise TA: Breast cancer metastasis to bone: Mechanisms of osteolysis and implications for therapy. J Mammary Gland Biol Neoplasia. 10:169–180. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Kingsley LA, Fournier PG, Chirgwin JM and Guise TA: Molecular biology of bone metastasis. Mol Cancer Ther. 6:2609–2617. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Li M, Amizuka N, Takeuchi K, Freitas PH, Kawano Y, Hoshino M, Oda K, Nozawa-Inoue K and Maeda T: Histochemical evidence of osteoclastic degradation of extracellular matrix in osteolytic metastasis originating from human lung small carcinoma (SBC-5) cells. Microsc Res Tech. 69:73–83. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Li M, Sasaki T, Ono K, de Freitas PH, Sobhan U, Kojima T, Shimomura J, Oda K and Amizuka N: Distribution of macrophages, osteoclasts and the B-lymphocyte lineage in osteolytic metastasis of mouse mammary carcinoma. Biomed Res. 28:127–137. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Jacob K, Webber M, Benayahu D and Kleinman HK: Osteonectin promotes prostate cancer cell migration and invasion: A possible mechanism for metastasis to bone. Cancer Res. 59:4453–4457. 1999.PubMed/NCBI

8 

Lynch CC and Matrisian LM: Matrix metalloproteinases in tumor-host cell communication. Differentiation. 70:561–573. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Nannuru KC, Futakuchi M, Varney ML, Vincent TM, Marcusson EG and Singh RK: Matrix metalloproteinase (MMP)-13 regulates mammary tumor-induced osteolysis by activating MMP9 and transforming growth factor-beta signaling at the tumor-bone interface. Cancer Res. 70:3494–3504. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Egeblad M and Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2:161–174. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Scherer RL, Mclntyre JO and Matrisian LM: Imaging matrix metalloproteinases in cancer. Cancer Metastasis Rev. 27:679–690. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Lee J, Weber M, Mejia S, Bone E, Watson P and Orr W: A matrix metalloproteinase inhibitor, batimastat, retards the development of osteolytic bone metastases by MDA-MB-231 human breast cancer cells in Balb C nu/nu mice. Eur J Cancer. 37:106–113. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Weber MH, Lee J and Orr FW: The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. Int J Oncol. 20:299–303. 2002.PubMed/NCBI

14 

Monteiro-Amado F, Castro-Silva II, Lima CJ, Soares FA, Kowalski LP and Granjeiro JM: Immunohistochemical evaluation of MMP-2, MMP-9 and CD31/microvascular density in squamous cell carcinomas of the floor of the mouth. Braz Dent J. 24:3–9. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Ohshiba T, Miyaura C, Inada M and Ito A: Role of RANKL-induced osteoclast formation and MMP-dependent matrix degradation in bone destruction by breast cancer metastasis. Br J Cancer. 88:1318–1326. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Morrison C, Mancini S, Cipollone J, Kappelhoff R, Roskelley C and Overall C: Microarray and proteomic analysis of breast cancer cell and osteoblast co-cultures: Role of osteoblast matrix metalloproteinase (MMP)-13 in bone metastasis. J Biol Chem. 286:34271–34285. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Lafleur MA, Drew AF, de Sousa EL, Blick T, Bills M, Walker EC, Williams ED, Waltham M and Thompson EW: Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts: A major induction of stromal MMP-13. Int J Cancer. 114:544–554. 2005. View Article : Google Scholar

18 

Huang S, Van Arsdall M, Tedjarati S, McCarty M, Wu W, Langley R and Fidler IJ: Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J Natl Cancer Inst. 94:1134–1142. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Björklund M and Koivunen E: Gelatinase-mediated migration and invasion of cancer cells. Biochim Biophys Acta. 1755:37–69. 2005.PubMed/NCBI

20 

Li M, Hasegawa T, Hogo H, Tatsumi S, Liu Z, Guo Y, Sasaki M, Tabata C, Yamamoto T, Ikeda K and Amizuka N: Histological examination on osteoblastic activities in the alveolar bone of transgenic mice with induced ablation of osteocytes. Histol Histopathol. 28:327–335. 2013.PubMed/NCBI

21 

Tsunoda M and Sharma RP: Modulation of tumor necrosis factor alpha expression in mouse brain after exposure to aluminum in drinking water. Arch Toxicol. 73:419–426. 1999. View Article : Google Scholar

22 

Sasaki E, Tsunoda N, Hatanaka Y, Mori N, Iwata H and Yatabe Y: Breast-specific expression of MGB1/mammaglobin: An examination of 480 tumors from various organs and clinicopathological analysis of MGB1-positive breast cancers. Mod Pathol. 20:208–214. 2007. View Article : Google Scholar

23 

Slattery ML, John E, Torres-Mejia G, Stern M, Lundgreen A, Hines L, Giuliano A, Baumgartner K, Herrick J and Wolff RK: Matrix metalloproteinase genes are associated with breast cancer risk and survival: The Breast Cancer Health Disparities Study. PLoS One. 8:e631652013. View Article : Google Scholar : PubMed/NCBI

24 

McCawley LJ and Matrisian LM: Matrix metalloproteinases: They're not just for matrix anymore! Curr Opin Cell Biol. 13:534–540. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Nutter F, Holen I, Brown HK, Cross SS, Evans CA, Walker M, Coleman RE, Westbrook JA, Selby PJ, Brown JE and Ottewell PD: Different molecular profiles are associated with breast cancer cell homing compared with colonisation of bone: Evidence using a novel bone-seeking cell line. Endocr Relat Cancer. 21:327–341. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Yin JJ, Selander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R, Massagué J, Mundy GR and Guise TA: TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest. 103:197–206. 1999. View Article : Google Scholar : PubMed/NCBI

27 

Woodward JK, Holen I, Coleman RE and Buttle DJ: The roles of proteolytic enzymes in the development of tumour-induced bone disease in breast and prostate cancer. Bone. 41:912–927. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Balbín M, Pendás AM, Uría JA, Jiménez MG, Freije JP and López-Otín C: Expression and regulation of collagenase-3 (MMP-13) in human malignant tumors. APMIS. 107:45–53. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Ni X, Xia T, Zhao Y, Zhou W, Wu N, Liu X, Ding Q, Zha X, Sha J and Wang S: Downregulation of miR-106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2. Cancer Sci. 105:18–25. 2014. View Article : Google Scholar

30 

Mastro AM, Gay CV, Welch DR, Donahue HJ, Jewell J, Mercer R, DiGirolamo D, Chislock EM and Guttridge K: Breast cancer cells induce osteoblast apoptosis: A possible contributor to bone degradation. J Cell Biochem. 91:265–276. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu B, Cui J, Sun J, Li J, Han X, Guo J, Yi M, Amizuka N, Xu X, Li M, Li M, et al: Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells. Mol Med Rep 14: 1099-1106, 2016.
APA
Liu, B., Cui, J., Sun, J., Li, J., Han, X., Guo, J. ... Li, M. (2016). Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells. Molecular Medicine Reports, 14, 1099-1106. https://doi.org/10.3892/mmr.2016.5374
MLA
Liu, B., Cui, J., Sun, J., Li, J., Han, X., Guo, J., Yi, M., Amizuka, N., Xu, X., Li, M."Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells". Molecular Medicine Reports 14.2 (2016): 1099-1106.
Chicago
Liu, B., Cui, J., Sun, J., Li, J., Han, X., Guo, J., Yi, M., Amizuka, N., Xu, X., Li, M."Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells". Molecular Medicine Reports 14, no. 2 (2016): 1099-1106. https://doi.org/10.3892/mmr.2016.5374
Copy and paste a formatted citation
x
Spandidos Publications style
Liu B, Cui J, Sun J, Li J, Han X, Guo J, Yi M, Amizuka N, Xu X, Li M, Li M, et al: Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells. Mol Med Rep 14: 1099-1106, 2016.
APA
Liu, B., Cui, J., Sun, J., Li, J., Han, X., Guo, J. ... Li, M. (2016). Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells. Molecular Medicine Reports, 14, 1099-1106. https://doi.org/10.3892/mmr.2016.5374
MLA
Liu, B., Cui, J., Sun, J., Li, J., Han, X., Guo, J., Yi, M., Amizuka, N., Xu, X., Li, M."Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells". Molecular Medicine Reports 14.2 (2016): 1099-1106.
Chicago
Liu, B., Cui, J., Sun, J., Li, J., Han, X., Guo, J., Yi, M., Amizuka, N., Xu, X., Li, M."Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells". Molecular Medicine Reports 14, no. 2 (2016): 1099-1106. https://doi.org/10.3892/mmr.2016.5374
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