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Background: Metastasis is a multi-step processes wherein tumor cells must be able to move from the primary tumor, disseminate throughout the body, and survive to grow in the ectopic locale. During the initial invasion stage, prostate carcinoma cells undergo epithelial mesenchymal-like transition with gain of mesencyhmal marker N-cadherin, and loss of epithelial marker E-cadherin. This switch in cell adhesion expression is thought to enable invasion and dissemination. Recently, several reports have shown that E-cadherin is reexpressed in met static tumors in various cancers including human prostate cancer. This suggests that EMT is not a linear progression, but transient transition conferring survival advantage to the metastasizing cancer cell. Therefore we sought to examine the role of N-cadherin expression in relation to E-cadherin reexpression within bone marrow stromal microenvironment.

Methods: We utilized a human prostate EMT model containing lineage derived ARCaP E cells (express epithelial markers) and ARCaP M cells (express mesencyhmal markers) to delineate EMT associated events during metastasis. ARCaP E & M cells were cocultured with HS-27a human bone marrow cells for various time periods.

Results: Immunocytochemistry of coculture revealed that ARCaP E & M and HS-27a cells express N-cadherin, without E-cadherin expression at day 1 and 2. However, as cocultures persist to day 4 and 6, N-cadherin expression remains in HS-27a cells; however is loss in both ARCaP E & M cells. This changes in cell adhesion expression were not seen in single cultures both cell types. Cell adhesion assay (CAFCA) demonstrated that N-cadherin siRNA pretreatment abrogated attachment of both ARCaP E & M cells to HS-27a cells.

Conclusion: Both ARCaP E & M utilize N-cadherin to adhere to bone marrow stromal cells. However, this expression is transient with E-cadherin predominantly expressed at later time periods. Therefore, we conclude that ARCaP E & M cells exhibit phenotypic variability throughout tumor progression which is modulated by the tumor microenvironment

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA