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BMP4 Promotes Prostate Tumor Growth in Bone through Osteogenesis
- Source :
- Cancer Research. 71:5194-5203
- Publication Year :
- 2011
- Publisher :
- American Association for Cancer Research (AACR), 2011.
-
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, MDA-PCa-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 MDA-PCa-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. Cancer Res; 71(15); 5194–203. ©2011 AACR.
- Subjects :
- Male
Cancer Research
Pathology
medicine.medical_specialty
medicine.medical_treatment
Bone Neoplasms
Bone Morphogenetic Protein 4
Mice, SCID
Adenocarcinoma
urologic and male genital diseases
Bone morphogenetic protein
Article
Mice
Prostate cancer
Subcutaneous Tissue
Osteogenesis
Prostate
Cell Line, Tumor
medicine
Animals
Humans
Bone morphogenetic protein receptor
skin and connective tissue diseases
Autocrine signalling
Bone Morphogenetic Protein Receptors, Type I
Osteoblasts
business.industry
Ossification, Heterotopic
Prostatic Neoplasms
Osteoblast
medicine.disease
Xenograft Model Antitumor Assays
Recombinant Proteins
Neoplasm Proteins
Autocrine Communication
Pyrimidines
medicine.anatomical_structure
Cytokine
Oncology
Bone morphogenetic protein 4
Culture Media, Conditioned
Cancer research
Cytokines
Intercellular Signaling Peptides and Proteins
Pyrazoles
business
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....f6a318f125574f3e89530eaca4ef80bc