Introduction: Epidemiological evidence suggests that saturated fatty acid has a role in prostate cancer progression; however underlying mechanisms remain unknown. Here, we conducted a comprehensive omics analysis to investigate candidate molecules associated with saturated fat-induced prostate cancer (PCa) progression.
Methods: TRAMP-C2 cells were subcutaneously injected into two groups of C57BL6 mice: the lard diet (LD) group, which was fed isocaloric saturated fatty acid, and the fish oil diet (FOD) group, which was fed polyunsaturated fatty acid. We performed an oligonucleotide microarray with the Affymetrix Gene Chip Mouse Gene 2.0 ST Array and proteomic analysis using nano-liquid chromatography-tandem mass spectrometry using xenograft tumors and validated the result by western blotting and immunohistochemistry. The cell proliferation and mRNA levels of CRABP2 in two PCa cell lines cultured with mice serum were assessed by performing an MTT cell assay and quantitative real-time polymerase chain reaction. The effect of CRABP2 on survival in PCa patients was evaluated by reviewing data from The Cancer Genome Atlas database.
Results: The mean body weight of the LD group tend to be higher than that of the LD group (p = 0.066). Subcutaneous tumor volume were significantly higher in the LD group than the FOD group (p = 0.044). One hundred fifty-three up- and 120 downregulated genes and 734 up- and 1514 downregulated proteins with >1.5-fold changes were identified in the LD group. Multi-omics approach showed 32 candidate molecules which have the potential to be highly associated with saturated fatty acid diet-induced prostate cancer progression. In the molecules, CRABP2 was selected as the most candidate molecule. The higher expression of CRABP2 in xenografts of the LD group was validated by western blotting and immunohistochemistry. PCa cells cultured in a medium containing LD mouse serum were associated with significantly higher cell proliferation rates and higher CRABP2 expression levels than those of PCa cells cultured in FOD. Overall survival significantly worse in the patients with altered CRABP2 than in those with unaltered CRABP2 (p < 0.001).
Conclusion: Saturated fatty acid-accelerated PCa growth was enhanced by CRABP2. CRABP2 may be a key regulator of diet-induced PCa progression and a novel therapeutic target for PCa. A low saturated fat diet in males may be encouraged.
Citation Format: Hiromi Sato, Shintarao Narita, Masanori Ishida, Soki Kashima, Ryohei Yamamoto, Atsushi Koizumi, Taketoshi Nara, Kazuyuki Numakura, Mitsuru Saito, Shigeru Satoh, Naoshi Dohmae, Tomonori Habuchi. Cellular retinoic acid-binding protein 2 enhances saturated fatty acid-induced prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2662.