Dietary Fructose Promotes Prostate Cancer Growth
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 24, 2021
- Source ID
- 10.1158/0008-5472.can-19-0456
Entities
People
- Alejandro S. Godoy
- Carolina E. Echeverría
- Catalina A. Asencio-barría
- Daniela V. Carreño
- Francisco Nualart
- Gonzalo A. Mayorga-Weber
- Ignacio F. San Francisco
- Javier F. Cerda-infante
- Loreto P. Véliz
- Maite A Castro
- Manuel A. Varas-godoy
- Nibaldo C. Inestrosa
- Néstor B. Corro
- Pablo A. Rojas
- Paula Sotomayor
- Pedro A. Cisternas
- Verónica A. Torres-estay
- Viviana P. Montecinos
Organizations
- CONICYT
- Chamber Music America
- Howard Hughes Medical Institute
- National Fund for Scientific and Technological Development
- Roswell Park Comprehensive Cancer Center
- San Sebastián University
- United States Department of Defense
- Universidad de los Andes