BMP4 promotes prostate tumor growth in bone through osteogenesis

Yu Chen Lee, Chien Jui Cheng, Mehmet A. Bilen, Jing Fang Lu, Robert L. Satcher, Li Yuan Yu-Lee, Gary E. Gallick, Sankar N. Maity, Sue Hwa Lin

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Abstract

Induction of new bone formation is frequently seen in the bone lesions from prostate cancer. However, whether osteogenesis is necessary for prostate tumor growth in bone is unknown. Recently, 2 xenografts, MDAPCa- 118b and MDA-PCa-133, were generated from prostate cancer bone metastases. When implanted subcutaneously in severe combined immunodeficient (SCID) mice, MDA-PCa-118b induced strong ectopic bone formation while MDA-PCa-133 did not. To identify the factors that are involved in bone formation, we compared the expression of secreted factors (secretome) from MDA-PCa-118b and MDA-PCa-133 by cytokine array. We found that the osteogenic MDA-PCa-118b xenograft expressed higher levels of bone morphogenetic protein BMP4 and several cytokines including interleukin-8, growth-related protein (GRO), and CCL2. We showed that BMP4 secreted from MDA-PCa-118b contributed to about a third of the osteogenic differentiation seen in MDAPCa- 118b tumors. The conditioned media from MDA-PCa-118b induced a higher level of osteoblast differentiation, which was significantly reduced by treatment with BMP4 neutralizing antibody or the small molecule BMP receptor 1 inhibitor LDN-193189. BMP4 did not elicit an autocrine effect on MDA-PCa-118b, which expressed low to undetectable levels of BMP receptors. Treatment of SCID mice bearing MDA-PCa-118b tumors with LDN-193189 significantly reduced tumor growth. Thus, these studies support a role of BMP4-mediated osteogenesis in the progression of prostate cancer in bone.

Original languageEnglish
Pages (from-to)5194-5203
Number of pages10
JournalCancer Research
Volume71
Issue number15
DOIs
Publication statusPublished - Aug 1 2011

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Bone Development
Osteogenesis
Prostate
Bone Morphogenetic Protein Receptors
Bone Neoplasms
Prostatic Neoplasms
SCID Mice
Neoplasms
Heterografts
Cytokines
Bone Morphogenetic Proteins
Conditioned Culture Medium
Growth
Neutralizing Antibodies
Osteoblasts
Interleukin-8
Neoplasm Metastasis
Bone and Bones
Proteins
LDN 193189

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lee, Y. C., Cheng, C. J., Bilen, M. A., Lu, J. F., Satcher, R. L., Yu-Lee, L. Y., ... Lin, S. H. (2011). BMP4 promotes prostate tumor growth in bone through osteogenesis. Cancer Research, 71(15), 5194-5203. https://doi.org/10.1158/0008-5472.CAN-10-4374

BMP4 promotes prostate tumor growth in bone through osteogenesis. / Lee, Yu Chen; Cheng, Chien Jui; Bilen, Mehmet A.; Lu, Jing Fang; Satcher, Robert L.; Yu-Lee, Li Yuan; Gallick, Gary E.; Maity, Sankar N.; Lin, Sue Hwa.

In: Cancer Research, Vol. 71, No. 15, 01.08.2011, p. 5194-5203.

Research output: Contribution to journalArticle

Lee, YC, Cheng, CJ, Bilen, MA, Lu, JF, Satcher, RL, Yu-Lee, LY, Gallick, GE, Maity, SN & Lin, SH 2011, 'BMP4 promotes prostate tumor growth in bone through osteogenesis', Cancer Research, vol. 71, no. 15, pp. 5194-5203. https://doi.org/10.1158/0008-5472.CAN-10-4374
Lee, Yu Chen ; Cheng, Chien Jui ; Bilen, Mehmet A. ; Lu, Jing Fang ; Satcher, Robert L. ; Yu-Lee, Li Yuan ; Gallick, Gary E. ; Maity, Sankar N. ; Lin, Sue Hwa. / BMP4 promotes prostate tumor growth in bone through osteogenesis. In: Cancer Research. 2011 ; Vol. 71, No. 15. pp. 5194-5203.
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