Differential Expression of Glucose Transporters and Hexokinases in Prostate Cancer with a Neuroendocrine Gene Signature: A Mechanistic Perspective for 18F-FDG Imaging of PSMA-Suppressed Tumors

Martin K. Bakht; Jessica M. Lovnicki; Janice Tubman; Keith F. Stringer; Jonathan Chiaramonte; Michael R. Reynolds; Iulian Derecichei; Rosa-Maria Ferraiuolo; Bre-Anne Fifield; Dorota Lubanska; So Won Oh; Gi Jeong Cheon; Cheol Kwak; Chang Wook Jeong; Keon Wook Kang; John F. Trant; Colm Morrissey; Ilsa M. Coleman; Yuzhuo Wang; Hojjat Ahmadzadehfar; Xuesen Dong; Lisa A. Porter

doi:10.2967/jnumed.119.231068

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FIGURE 1.
AR-negative subsets of mCRPC in UW cohort (3) have suppressed expression of FOLH1 and differential expression of SLC2A and hexokinase genes. (A) Heat-map plot of expression levels of SLC2A family members, hexokinase genes, AR, FOLH1, and neuroendocrine markers sorted on the basis of nearest neighbors clustering to AR. (B, C, and D) Box–whisker plots showing expression of FOLH1, GCK, and SLC2A12, respectively.
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FIGURE 2.
NELPC subset of Memorial Sloan Kettering Cancer Center cohort (24) displays shorter time to BCR (A), greater prevalence of metastatic and high Gleason score specimens (B), and lack of AR response (C). (D) Violin plots compare distribution of SLC2A12, GCK, and FOLH1 expressions in NELPC and AdPC subsets. BCR = biochemical recurrence; ES = enrichment score; FDR = false discovery rate.
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FIGURE 3.
NEPC PDX models have suppressed expression of FOLH1 and differential expressions of SLC2A12 and GCK. (A) Transcription of studied genes during progression to NEPC and correlation with AR. (B) Expression of studied genes in PDX models.
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FIGURE 4.
Neuroendocrine-induced LNCaP cell line represents higher glucose uptake and differential protein levels of glucokinase and GLUT12. (A and B) Western blot analyses of protein levels. (C and D) Quantification of GB2-Cy3 uptake and representative images of LNCaP cells. Scale bar = 200 μm.
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FIGURE 5.
Neuroendocrine-induced LNCaP cell line xenografts represent higher glucose uptake in zebrafish model. (A) Schematic of experiment. (B and C) Quantification of GB2-Cy3 uptake and representative images of embryos injected with different LNCaP cells. Arrowheads show injection sites. Scale bar = 200 μm.