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Abstract B10: A novel mechanism of prostate cancer metastasis through the PDGF D/β-PDGFR axis
Cancer metastasis is a multi-step process permitting malignant cells to invade into a secondary niche. Prostate cancer has a high prevalence of bone metastasis where 90% of diagnosed cases exhibit metastatic bone lesions. Analysis of these metastatic tissues revealed that PDGFRβ (platelet-growth fac...
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Published in: | Cancer research (Chicago, Ill.) Ill.), 2009-12, Vol.69 (23_Supplement), p.B10-B10 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Cancer metastasis is a multi-step process permitting malignant cells to invade into a secondary niche. Prostate cancer has a high prevalence of bone metastasis where 90% of diagnosed cases exhibit metastatic bone lesions. Analysis of these metastatic tissues revealed that PDGFRβ (platelet-growth factor receptor β) is upregulated and activated in 80% of the cases. This receptor was thought to be stimulated by its classical ligand PDGF B. However, within bone metastatic prostate cancer, PDGF B is not detected, suggesting another ligand may exist for PDGFR β. Recently, a new PDGF family member, PDGF D, was identified and shown to bind to and activate PDGFR β. Using Oncomine data analysis and immunohistochemical analysis, we demonstrated upregulation of PDGF D in metastatic prostate cancer. To investigate the role of PDGF D in bone metastasis, we established several prostate cancer cell lines engineered to overexpress PDGF D. We observed an increase in prostate carcinoma cell migration as well as adhesion on osteoblast deposited matrix in response to PDGF D upregulation. Cell surface integrins are known to play a crucial role in cell migration and adhesion. Our studies revealed that PDGF D overexpression modulated α1 and α3 expression to mediate the cancer cell malignant phenotype. In the intratibial metastatic mouse model, PDGF D enhanced prostate cancer tumorigenesis and resulted in osteoblastic lesions. Consistent with our in vivo findings, we found that PDGF D supports osteoblast proliferation and differentiation in vitro. Taken together, we propose that PDGF D contributes to prostate cancer bone metastasis through tumor cell surface integrin modulation and stimulation of stromal components within the bone microenvironment.
Citation Information: Cancer Res 2009;69(23 Suppl):B10. |
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ISSN: | 0008-5472 1538-7445 |
DOI: | 10.1158/0008-5472.FBCR09-B10 |