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논문 기본 정보

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학술저널
저자정보
Kim, Bomi (Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University) Nam, Sorim (Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University) Lim, Ji Hyun (Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University) Lim, Jong-Seok (Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University)
저널정보
한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제24권 제1호
발행연도
2016.1
수록면
9 - 18 (10page)

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Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.
#NDRG2 #ICAM1 #Osteoclast #Osteolytic metastasis #Tumor environment

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참고문헌 (49)

참고문헌 신청
Boyce, B. F / 2013 / Advances in the regulation of osteoclasts and os17teoclast functions / J. Dent. Res 92:860~867 google schola Boyle, W. J / 2003 / Osteoclast differentiation and activation / Nature 423:337~342 google schola Choi, S. C / 2008 / Expression of human NDRG2 by myeloid dendritic cells inhibits down-regulation of activated leukocyte cell adhesion molecule (ALCAM) and contributes to maintenance of T cell stimulatory activity / J. Leukoc. Biol 83:89~98 google schola Clezardin, P / 2009 / Integrins in bone metastasis formation and potential therapeutic implications / Curr. Cancer Drug Targets 9:801~806 google schola Coleman, R. E / 2001 / Metastatic bone disease: clinical features, pathophysiology and treatment strategies / Cancer Treat. Rev 27:165~176 google schola

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