Runx2 association with progression of prostate cancer in patients

Mechanisms mediating bone osteolysis and osteoblastic metastatic lesions

J. Akech, J. J. Wixted, K. Bedard, M. Van Der Deen, S. Hussain, T. A. Guise, Andre J van Wijnen, J. L. Stein, L. R. Languino, D. C. Altieri, J. Pratap, E. Keller, G. S. Stein, J. B. Lian

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)811-821
Number of pages11
JournalOncogene
Volume29
Issue number6
DOIs
StatePublished - Feb 2010
Externally publishedYes

Fingerprint

Osteolysis
Prostatic Neoplasms
Bone and Bones
Neoplasms
Prostate
Neoplasm Metastasis
Parathyroid Hormone-Related Protein
Bone Neoplasms
Osteopontin
Bone Diseases
Coculture Techniques
Osteoblasts
Interleukin-8
Osteogenesis
Vascular Endothelial Growth Factor A
Small Interfering RNA
Cell Movement
Adenocarcinoma
Growth
Genes

Keywords

  • Bone metastasis
  • Prostate cancer tissue arrays
  • Runx2

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Akech, J., Wixted, J. J., Bedard, K., Van Der Deen, M., Hussain, S., Guise, T. A., ... Lian, J. B. (2010). Runx2 association with progression of prostate cancer in patients: Mechanisms mediating bone osteolysis and osteoblastic metastatic lesions. Oncogene, 29(6), 811-821. https://doi.org/10.1038/onc.2009.389

Runx2 association with progression of prostate cancer in patients : Mechanisms mediating bone osteolysis and osteoblastic metastatic lesions. / Akech, J.; Wixted, J. J.; Bedard, K.; Van Der Deen, M.; Hussain, S.; Guise, T. A.; van Wijnen, Andre J; Stein, J. L.; Languino, L. R.; Altieri, D. C.; Pratap, J.; Keller, E.; Stein, G. S.; Lian, J. B.

In: Oncogene, Vol. 29, No. 6, 02.2010, p. 811-821.

Research output: Contribution to journalArticle

Akech, J, Wixted, JJ, Bedard, K, Van Der Deen, M, Hussain, S, Guise, TA, van Wijnen, AJ, Stein, JL, Languino, LR, Altieri, DC, Pratap, J, Keller, E, Stein, GS & Lian, JB 2010, 'Runx2 association with progression of prostate cancer in patients: Mechanisms mediating bone osteolysis and osteoblastic metastatic lesions', Oncogene, vol. 29, no. 6, pp. 811-821. https://doi.org/10.1038/onc.2009.389
Akech, J. ; Wixted, J. J. ; Bedard, K. ; Van Der Deen, M. ; Hussain, S. ; Guise, T. A. ; van Wijnen, Andre J ; Stein, J. L. ; Languino, L. R. ; Altieri, D. C. ; Pratap, J. ; Keller, E. ; Stein, G. S. ; Lian, J. B. / Runx2 association with progression of prostate cancer in patients : Mechanisms mediating bone osteolysis and osteoblastic metastatic lesions. In: Oncogene. 2010 ; Vol. 29, No. 6. pp. 811-821.
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