β2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis

Wen Chin Huang, Daqing Wu, Zhihui Xie, Haiyen E. Zhau, Takeo Nomura, Majd Zayzafoon, Jan Pohl, Chia Ling Hsieh, M. Neale Weitzmann, Mary C. Farach-Carson, Leland W.K. Chung

Research output: Contribution to journalArticle

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Abstract

The protein factor β2-microglobulin (β2M), purified from the conditioned medium of human prostate cancer cell lines, stimulated growth and enhanced osteocalcin (OC) and bone sialoprotein (BSP) gene expression in human prostate cancer cells by activating a cyclic AMP (cAMP)-dependent protein kinase A signaling pathway. When β2M was overexpressed in prostate cancer cells, it induced explosive tumor growth in mouse bone through increased phosphorylated cAMP-responsive element binding protein (CREB) and activated CREB target gene expression, including OC, BSP, cyclin A, cyclin D1, and vascular endothelial growth factor. Interrupting the β2M downstream signaling pathway by injection of the β2M small interfering RNA liposome complex produced an effective regression of previously established prostate tumors in mouse bone through increased apoptosis as shown by immunohistochemistry and activation of caspase-9, caspase-3, and cleavage of poly(ADP-ribose) polymerase. These results suggest that β2M signaling is an attractive new therapeutic target for the treatment of lethal prostate cancer bone metastasis.

Original languageEnglish (US)
Pages (from-to)9108-9116
Number of pages9
JournalCancer Research
Volume66
Issue number18
DOIs
StatePublished - Sep 15 2006

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Bone Neoplasms
Prostatic Neoplasms
Intercellular Signaling Peptides and Proteins
Integrin-Binding Sialoprotein
Neoplasm Metastasis
Osteocalcin
Cyclic AMP-Dependent Protein Kinases
Carrier Proteins
Gene Expression
Bone and Bones
Cyclin A
Poly(ADP-ribose) Polymerases
Caspase 9
Cyclin D1
Conditioned Culture Medium
Growth
Liposomes
Caspase 3
Cyclic AMP
Vascular Endothelial Growth Factor A

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Huang, W. C., Wu, D., Xie, Z., Zhau, H. E., Nomura, T., Zayzafoon, M., ... Chung, L. W. K. (2006). β2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis. Cancer Research, 66(18), 9108-9116. https://doi.org/10.1158/0008-5472.CAN-06-1996

β2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis. / Huang, Wen Chin; Wu, Daqing; Xie, Zhihui; Zhau, Haiyen E.; Nomura, Takeo; Zayzafoon, Majd; Pohl, Jan; Hsieh, Chia Ling; Weitzmann, M. Neale; Farach-Carson, Mary C.; Chung, Leland W.K.

In: Cancer Research, Vol. 66, No. 18, 15.09.2006, p. 9108-9116.

Research output: Contribution to journalArticle

Huang, WC, Wu, D, Xie, Z, Zhau, HE, Nomura, T, Zayzafoon, M, Pohl, J, Hsieh, CL, Weitzmann, MN, Farach-Carson, MC & Chung, LWK 2006, 'β2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis', Cancer Research, vol. 66, no. 18, pp. 9108-9116. https://doi.org/10.1158/0008-5472.CAN-06-1996
Huang, Wen Chin ; Wu, Daqing ; Xie, Zhihui ; Zhau, Haiyen E. ; Nomura, Takeo ; Zayzafoon, Majd ; Pohl, Jan ; Hsieh, Chia Ling ; Weitzmann, M. Neale ; Farach-Carson, Mary C. ; Chung, Leland W.K. / β2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis. In: Cancer Research. 2006 ; Vol. 66, No. 18. pp. 9108-9116.
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