Fascin Regulates Prostate Cancer Cell Invasion and Is Associated with Metastasis and Biochemical Failure in Prostate Cancer
AD Darnel, E Behmoaram, RT Vollmer, J Corcos, K Bijian, K Sircar, J Su, J Jiao, MA Alaoui-Jamali, TA Bismar. McGill University and Lady Davis Cancer Institute, Montreal, QC, Canada; McGill University, Montreal, QC, Canada; VA and Duke University Medical Centers, Durham, NC; University of Calgary, Calgary, AB, Canada
Background: Prostate cancer (PCA) metastasis to secondary organs is considered an initial event in the development of hormone refractory disease and remains the major cause of death among PCA patients. In this study, we investigated the role of fascin, a cytoskeleton actin-bundling protein involved in the formation of filopodia and cell migration, in prostate cancer progression.
Design: Fascin protein expression was examined by immunohistochemistry in a cohort of 196 patients with localized PCA and across several stages of disease progression, including hormone refractory disease. Cellular changes were also assessed in vitro and in vivo in DU145 PCA cell line using fascin gene silencing.
Results: Fascin epithelial expression was significantly upregulated in localized and hormone refractory prostate cancer compared to benign prostate tissue (p<0.05). Furthermore, high fascin expression was associated with an increased rate of PSA recurrence following radical prostatectomy (p=0.075) signifying more aggressive clinical course, thus, supporting a function for fascin in PCA progression. In cellular models, fascin gene silencing using siRNA in the androgen-independent PCA cell line DU145 decreased cell motility and invasiveness while increasing cell adhesive properties. In addition, fascin siRNA expressing DU145 cells implanted orthotopically in mouse prostate showed significantly decreased growth (p<0.005) and drastically prevented the formation of lymph node metastases (p<0.001) compared to their matched controls.
Conclusions: Our data demonstrate a function of fascin in the regulation of PCA progression and emphasizes the importance of fascin as a prognostic marker for aggressive disease and as a potential therapeutic target for advanced androgen independent disease.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 8:45 AM
Platform Session: Section A, Tuesday Morning