Fascin-1, a prominent actin-bundling protein, is found to be upregulated in several human carcinomas. While it is accepted that Fascin-1 expression correlates with poor clinical outcome and decreased survival in various carcinomas, its role in sarcoma such as osteosarcoma (OS) remains unknown. In the present study, we evaluated the prognostic value and biological relevance of Fascin-1 in OS. The correlation between Fascin-1 expression and the outcome of OS patients was determined by immunohistochemistry analysis of Fascin-1 expression in a tissue microarray of OS tissue specimens collected during primary tumor resection. To examine the effect of Fascin-1, shRNA and overexpression technology to alter Fascin-1 levels in OS cells were used in cellular assays as well as in intratibial xenograft OS models in SCID mice. Kaplan-Meier survival analysis of Fascin-1 expression in OS tumor specimens revealed a direct relationship between Fascin-1 expression and poor patient survival. Furthermore, overexpression of Fascin-1 in OS cells significantly increased their migratory capacity as well as the activity of the matrix metalloprotease MMP-9, known to be critical for the execution of metastasis. Finally, using relevant xenograft mouse models, orthotopic intratibial transplantation of two different OS cell lines overexpressing Fascin-1 promoted tumor growth and lung metastasis. Collectively, our findings demonstrate for the first time that Fascin-1 has considerable potential as a novel prognostic biomarker in OS, and suggest that targeting of Fascin-1 might be a new anti-metastatic strategy in OS patient treatment.

Is missing (Short communication)...

Objective: Abi, when used in conjunction with prednisone, is an established treatment for advanced PCa. Our goal was to explore the level of autophagy induced by Abi treatment, both alone and in combination with the autophagy inhibitor Chl, in a castrated mouse xenograft model. Methods: LNCaP cells were injected into the left and right sides of the back of nude mice that had been previously castrated. Mice were divided into four groups and treated daily with intraperitoneal injections of vehicle (control), Abi (10 mg/kg), Abi (10 mg/kg) combined with Chl (10 mg/kg), or Chl (10 mg/kg), and were monitored for periods of 2 and 3 weeks. Results: A significant reduction in tumor weight was observed in mice treated with the combination therapy, as opposed to those receiving vehicle control, Abi, or Chl alone. Mice receiving Abi + Chl exhibited reduced expression of ATG5, Beclin 1, and LC3 punctuations, along with an increase in P62, as determined by immunofluorescence and WES analysis. AR expression decreased significantly in all treatment groups compared to the control. PSMA expression was highest in the vehicle and combined treatment groups after 3 weeks, with a significant reduction observed with Chl treatment. Conclusions: These findings demonstrate that Abi + Chl treatment lowers autophagy levels and suppresses tumors more effectively than Abi alone.

Prostate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low PSMA surface expression can be a limitation for this promising diagnostic tool. Pharmacological induction of PSMA might be useful to further improve the detection rate of PSMA-based imaging. To achieve this, we tested dutasteride (Duta)—generally used for treatment of benign prostatic enlargement—and lovastatin (Lova)—a compound used to reduce blood lipid concentrations. We aimed to compare the individual effects of Duta and Lova on cell proliferation as well as PSMA expression. In addition, we tested if a combination treatment using lower concentrations of Duta and Lova can further induce PSMA expression. Our results show that a treatment with ≤1 μM Duta and ≥1 μM Lova lead to a significant upregulation of whole and cell surface PSMA expression in LNCaP, C4-2 and VCaP cells. Lower concentrations of Duta and Lova in combination (0.5 μM Duta + 0.5 μM Lova or 0.5 μM Duta + 1 μM Lova) were further capable of enhancing PSMA protein expression compared to a single compound treatment using higher concentrations in all tested cell lines (LNCaP, C4-2 and VCaP).