BMP4 Promotes Prostate Tumor Growth in Bone through Osteogenesis

2011/06/13 by Yu-Chen Lee, Chien-Jui Cheng, Mehmet Asım Bilen +8 · 26 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Autocrine signalling #Bone health and treatments #Bone morphogenetic protein #Bone morphogenetic protein 4 #Cancer #Cancer research #Chemistry #Endocrinology #Heterotopic Ossification and Related Conditions #Internal medicine #Medicine #Osteoblast #Pathology #Prostate #Prostate cancer #Receptor #TGF-β signaling in diseases

paper · pdf · doi:10.1158/0008-5472.can-10-4374

openalex publication_date 2011/06/13 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/01

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.

Cited by

• Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2
• Molecular classification of prostate cancer progression: foundation for marker-driven treatment of prostate cancer. [europepmc]
• Bone Morphogenetic Proteins stimulate mammary fibroblasts to promote mammary carcinoma cell invasion. [europepmc]
• Promoter hypomethylation of EpCAM-regulated bone morphogenetic protein gene family in recurrent endometrial cancer. [europepmc]
• Inhibition of BMP signaling suppresses metastasis in mammary cancer. [europepmc]
• Integrating Murine and Clinical Trials with Cabozantinib to Understand Roles of MET and VEGFR2 as Targets for Growth Inhibition of Prostate Cancer. [europepmc]
• BMP4 depletion by miR-200 inhibits tumorigenesis and metastasis of lung adenocarcinoma cells. [europepmc]
• Identification of Bone-Derived Factors Conferring De Novo Therapeutic Resistance in Metastatic Prostate Cancer. [europepmc]
• A 3D in vitro model of patient-derived prostate cancer xenograft for controlled interrogation of in vivo tumor-stromal interactions. [europepmc]
• The Drosophila Accessory Gland as a Model for Prostate Cancer and Other Pathologies. [europepmc]
• Targeting DNA Damage Response in Prostate Cancer by Inhibiting Androgen Receptor-CDC6-ATR-Chk1 Signaling. [europepmc]
• Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer. [europepmc]
• Proteomics Profiling of Exosomes from Primary Mouse Osteoblasts under Proliferation versus Mineralization Conditions and Characterization of Their Uptake into Prostate Cancer Cells. [europepmc]
• Enzalutamide and CXCR7 inhibitor combination treatment suppresses cell growth and angiogenic signaling in castration-resistant prostate cancer models. [europepmc]
• Bone Cell Activity in Clinical Prostate Cancer Bone Metastasis and Its Inverse Relation to Tumor Cell Androgen Receptor Activity. [europepmc]
• Role of Tumor-Derived Chemokines in Osteolytic Bone Metastasis. [europepmc]
• Osteoblastic Factors in Prostate Cancer Bone Metastasis. [europepmc]
• Androgen deprivation promotes neuroendocrine differentiation and angiogenesis through CREB-EZH2-TSP1 pathway in prostate cancers. [europepmc]
• Insights into the Role of Circadian Rhythms in Bone Metabolism: A Promising Intervention Target? [europepmc]
• Discovery of a natural small-molecule compound that suppresses tumor EMT, stemness and metastasis by inhibiting TGFβ/BMP signaling in triple-negative breast cancer. [europepmc]
• LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling. [europepmc]
• BMP3 suppresses colon tumorigenesis via ActRIIB/SMAD2-dependent and TAK1/JNK signaling pathways. [europepmc]
• The MAO inhibitors phenelzine and clorgyline revert enzalutamide resistance in castration resistant prostate cancer. [europepmc]
• Molecular mechanisms and clinical management of cancer bone metastasis. [europepmc]
• Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1-targeting miRNA-92a-1-5p. [europepmc]
• Mesenchymal and stem-like prostate cancer linked to therapy-induced lineage plasticity and metastasis. [europepmc]

Related

• Adrenal-derived factors drive progression of sclerotic prostate cancer in bone
• HE3235 Inhibits Growth of Castration-Resistant Prostate Cancer
• Interplay between bone marrow adiposity and bone resorption in RANKL‐mediated modelled osteoporosis
• Bone Marrow Cells Inhibit BMP-2-Induced Osteoblast Activity in the Marrow Environment
• RANK ligand is a prerequisite for cancer‐associated osteolytic lesions