Runx2 association with progression of prostate cancer in patients: mechanisms mediating bone osteolysis and osteoblastic metastatic lesions

被引：233

作者：

Akech, J. ^{[1
,2
]}

Wixted, J. J. ^{[2
,3
]}

Bedard, K. ^{[1
,2
]}

van der Deen, M. ^{[1
,2
]}

Hussain, S. ^{[1
,2
]}

Guise, T. A. ^{[4
]}

van Wijnen, A. J. ^{[1
,2
]}

Stein, J. L. ^{[1
,2
]}

Languino, L. R. ^{[2
,5
]}

Altieri, D. C. ^{[2
,5
]}

Pratap, J. ^{[1
,2
]}

Keller, E. ^{[6
]}

Stein, G. S. ^{[1
,2
]}

Lian, J. B. ^{[1
,2
]}

机构：

[1] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA

[2] Univ Massachusetts, Sch Med, Ctr Canc, Prostate Canc Discovery & Dev Program, Worcester, MA 01655 USA

[3] Univ Massachusetts, Sch Med, Dept Orthoped Surg & Rehabil, Worcester, MA 01655 USA

[4] Indiana Univ, Sch Med, Dept Internal Med, Indianapolis, IN USA

[5] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01655 USA

[6] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA

来源：

ONCOGENE | 2010年 / 29卷 / 06期

关键词：

Runx2; bone metastasis; prostate cancer tissue arrays; MATRIX METALLOPROTEINASES; TRANSCRIPTION FACTORS; TUMOR-CELLS; EXPRESSION; DIFFERENTIATION; INTERLEUKIN-8; SIALOPROTEIN; OSTEOCALCIN; ACTIVATION; PROMOTE;

D O I：

10.1038/onc.2009.389

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Runx2, a bone-specific transcriptional regulator, is abnormally expressed in highly metastatic prostate cancer cells. Here, we identified the functional activities of Runx2 in facilitating tumor growth and osteolysis. Our studies show that negligible Runx2 is found in normal prostate epithelial and non-metastatic LNCaP prostate cancer cells. In the intra-tibial metastasis model, high Runx2 levels are associated with development of large tumors, increased expression of metastasis-related genes (MMP9, MMP13, VEGF, Osteopontin) and secreted bone-resorbing factors (PTHrP, IL8) promoting osteolytic disease. Runx2 siRNA treatment of PC3 cells decreased cell migration and invasion through Matrigel in vitro, and in vivo shRunx2 expression in PC3 cells blocked their ability to survive in the bone microenvironment. Mechanisms of Runx2 function were identified in co-culture studies showing that PC3 cells promote osteoclastogenesis and inhibit osteoblast activity. The clinical significance of these findings is supported by human tissue microarray studies of prostate tumors at stages of cancer progression, in which Runx2 is expressed in both adenocarcinomas and metastatic tumors. Together these findings indicate that Runx2 is a key regulator of events associated with prostate cancer metastatic bone disease. Oncogene (2010) 29, 811-821; doi:10.1038/onc.2009.389; published online 16 November 2009

引用

页码：811 / 821

页数：11

共 44 条

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