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

• Published in: Clinical & experimental metastasis 2008-06, Vol.25 (4), p.377-388
• Main Authors: Morrissey, Colm, True, Lawrence D., Roudier, Martine P., Coleman, Ilsa M., Hawley, Sarah, Nelson, Peter S., Coleman, Roger, Wang, Ya-Chun, Corey, Eva, Lange, Paul H., Higano, Celestia S., Vessella, Robert L.
• Format: Article
• Language: English
• Subjects: Angiopoietin-1 - genetics; Angiopoietin-2 - genetics; Biomedical and Life Sciences; Biomedicine; Bone and Bones - metabolism; Calcium-Binding Proteins - genetics; Cancer Research; Factor VIIIa - genetics; Gene Expression Profiling; Hematology; Humans; Liver - metabolism; Lymphatic Metastasis; Male; Neovascularization, Physiologic; Oligonucleotide Array Sequence Analysis; Oncology; Plasminogen Activator Inhibitor 1 - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Research Paper; RNA-Binding Proteins - genetics; Surgical Oncology; Urokinase-Type Plasminogen Activator - genetics
• ISSN: 0262-0898; 1573-7276
• DOI: 10.1007/s10585-007-9116-4

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.