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Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastases

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Abstract

Our objective was to elucidate phenotypic differences between prostate cancer (PCa) liver, lymph node, and bone metastases. PCa metastases were obtained through a rapid tissue acquisition necropsy protocol. We grossly dissected metastatic foci from frozen samples and performed expression analyses using cDNA microarrays. Immunohistochemical analyses using a tissue microarray from thirty individuals with PCa metastases to lymph nodes, liver, and bone was used to confirm the gene expression changes associated with each metastatic site. Transcript alterations statistically-associated with bone metastases included increased expression of IBSP (Bone sialoprotein), F13A1 (factor XIII), and decreased expression of EFNA1 (ephrin-A1) and ANGPT2 (angiopoietin-2) when compared to liver and lymph node metastases. The metastasis-associated changes in proteins involved in coagulation and angiogenesis prompted further analysis of additional factors known to participate in the clotting cascade and blood vessel formation (angiopoitein-1, PAI-1, uPA, PAI-RBP-1 and hepsin). We also assessed tumor-associated microvessel density and distribution in liver, lymph node, and bone metastasis. Intense fibrin(ogen) and fibulin-1 staining was localized to epithelial cells at the periphery of metastatic tumors possibly to facilitate angiogenesis. The expression of hepsin, uPA, PAI-RBP1, PAI-1, and factor XIII may influence fibrinolysis and are regulated by the tumor microenvironment. The expression of angiopoietin-2 and apparent silencing of angiopoietin-1 in PCa bone, liver, and lymph node metastases may be critical for angiogenesis in this tumor type. In addition, the resulting tumor-associated microvessel density and distribution was significantly different between liver and bone metastasis possibly in response to the protein expression changes detailed above.

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Acknowledgments

We would sincerely like to thank the patients and their families who were willing to take part in the PCa rapid autopsy series. We would also like to thank the rapid autopsy teams, Dr. Janice Lai and Roman Gulati for their contributions to the manuscript, and Sue Hall and Deanna Gonzales for the clinical analyses. Finally, we would like to thank Dr. Joanne Heaton for the use of the PAI-RBP1 antibody. These studies were supported by the Department of Veterans Affair’s, the Department of Defense (DAMD170320033), the National Institutes of Health (PO1CA085859), (PCO41158) and (P50CA097186), the Richard M. Lucas Foundation and the Prostate Cancer Foundation.

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Authors and Affiliations

  1. Genitourinary Cancer Research Laboratory, Department of Urology, University of Washington, Box 356510, Seattle, WA, 98195, USA

    Colm Morrissey, Martine P. Roudier, Ya-Chun Wang, Eva Corey, Paul H. Lange & Robert L. Vessella

  2. Puget Sound VA Medical Center, Seattle, WA, USA

    Colm Morrissey & Robert L. Vessella

  3. Department of Pathology, University of Washington, Seattle, WA, USA

    Lawrence D. True

  4. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Ilsa M. Coleman, Sarah Hawley, Peter S. Nelson & Roger Coleman

  5. Department of Medicine, University of Washington, Seattle, WA, USA

    Celestia S. Higano

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  1. Colm Morrissey
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Correspondence to Colm Morrissey.

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Morrissey, C., True, L.D., Roudier, M.P. et al. Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastases. Clin Exp Metastasis 25, 377–388 (2008). https://doi.org/10.1007/s10585-007-9116-4

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  • DOI: https://doi.org/10.1007/s10585-007-9116-4

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