Clinical localization of primary tumors and sites of metastasis by PET is based on the enhanced cellular uptake of 2-deoxy-2-[18F]-fluoro-D-glucose (FDG). In prostate cancer, however, PET-FDG imaging has shown limited clinical applicability, suggesting that prostate cancer cells may utilize hexoses other than glucose, such as fructose, as the preferred energy source. Our previous studies suggested that prostate cancer cells overexpress fructose transporters, but not glucose transporters, compared with benign cells. Here, we focused on validating the functional expression of fructose transporters and determining whether fructose can modulate the biology of prostate cancer cells in vitro and in vivo. Fructose transporters, Glut5 and Glut9, were significantly upregulated in clinical specimens of prostate cancer when compared with their benign counterparts. Fructose levels in the serum of patients with prostate cancer were significantly higher than healthy subjects. Functional expression of fructose transporters was confirmed in prostate cancer cell lines. A detailed kinetic characterization indicated that Glut5 represents the main functional contributor in mediating fructose transport in prostate cancer cells. Fructose stimulated proliferation and invasion of prostate cancer cells in vitro. In addition, dietary fructose increased the growth of prostate cancer cell line-derived xenograft tumors and promoted prostate cancer cell proliferation in patient-derived xenografts. Gene set enrichment analysis confirmed that fructose stimulation enriched for proliferation-related pathways in prostate cancer cells. These results demonstrate that fructose promotes prostate cancer cell growth and aggressiveness in vitro and in vivo and may represent an alternative energy source for prostate cancer cells.
Nota bibliográficaFunding Information:
This work was supported by grants from the Department of Defense (W81XWH-12-1-0341 to A.S. Godoy), HHMI Janelia Visitor Program (JVS0028700 to M.A. Castro), FONDECYT (1161115 to A.S. Godoy), FONDECYT (1160724 to N.C. Inestrosa), FONDECYT (11140255 to P.C. Sotomayor), FONDECYT (11160651 to P.A. Cisternas), FONDECYT (1191620 to M.A. Castro), FONDECYT (1150397 to V.P. Montecinos), CMA BIO BIO PIA-Conicyt (ECM-12 to F.J. Nualart), Basal Center of Excellence in Aging and Regeneration (CONICYT-PFB12/2007 to N.C. Inestrosa), and fellowships from FONDECYT-Post-Doctoral (3160717 to D.V. Carreño), CONICYT-PhD (22140138 to V.A. Torres-Estay), CONICYT-PhD (21171084 to N.B. Corro), PhD Scholarship FAI-Universidad de los Andes-Chile (to C.E. Echeverría).
© 2021 American Association for Cancer Research.