Abstract: PD33-12
Sources of Funding: none

Introduction

Fatty acid binding protein 4 (FABP4) is a small FA chaperone molecule. FABP4 is highly expressed in adipocytes and macrophages affect the metabolic process, but the function of FABP4 in cancer including prostate cancer (PCa) is unclear. In the present study, we investigated the expression pattern and role of FABP4 in PCa and prostate stromal cells (PrSC).

Methods

The expression of FABP4 in PCa, PrSC and the conditioned medium were determined by the Western blotting, Immunohistochemistry and ELISA. Cytokine levels in the conditioned medium and serum was measured by the Human cytokines array kit. The metastatic and invasive PCa model was established by intraperitoneum injection of PC-3 M Luc-C6 cells into male 6-week-old Balb/c nu/nu mice, and the functional role of FABP4 was investigated.

Results

FABP4 was highly expressed and secreted in the PCa PC-3 cells, and stimulated the PrSC to secretion of proinflammatory cytokine IL-8 and IL-6. PrSC augmented PCa cell?invasiveness by the secretion of IL-6 and IL-8 in response to secreted FABP4 by PCa cells. In addition, FABP4 directly stimulated the PCa cell invasiveness by the upregulation of MMPs by activation of AKT and ERK signal pathways. PrSC and HFD condition increased the PCa cell invasiveness by the upregulation FABP4, IL-8 and MMPs in vivo. FABP4 was highly expressed in human PCa. The serum FABP4 levels was significantly higher in the PCa patients than normal individual (p = 0.001), and the levels of FABP4 was associated with the Gleason Score (GS, p = 0.018), and advanced PCa pathological T stage (pT, p = 0.022).

Conclusions

FABP4 was overexpressed and secreted in the PCa, and directly stimulated the PCa progression. PrSC was activated, and augmented the PCa invasiveness by the secretion of IL-6 and IL-8 in response to secreted FABP4 by PCa cells in the prostate stromal tumor microenvironment. FABP4 may be a useful therapeutic target for prostate cancer.

Funding

none