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

研究成果: 雜誌貢獻文章同行評審

93 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)5194-5203
頁數10
期刊Cancer Research
71
發行號15
DOIs
出版狀態已發佈 - 8月 1 2011

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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