Relationship of choline kinase expression assessed by choline-PET and prostate cancer cell aggressive phenotype

Objectives By noninvasive assessment of choline kinase expression, choline-PET may have utility to monitor aggressive tumor phenotype. Increased choline kinase expression is associated with aggressive tumor phenotype however it is not clear if this relationship differs in cancer cells representing different cancer disease state. In this study effect of choline kinase expression on tumor aggressive phenotype was studied in both early stage androgen-dependent prostate cancer (LNCaP) and later stage, androgen-independent disease (PC-3).

Methods [14C]choline uptake, cell population doubling time, cell migration and invasion, pro-migratory factor uPa expression, and anchorage independent growth was assessed as indices of tumor aggressive phenotype in control and choline kinase (ChKα) over-expressing LNCaP and PC-3 cells.

Results Overexpression of ChKα decreased cell proliferation rate and cell invasion potential of late stage PC-3 cells. On the other hand, in LNCaP cells, overexpression of ChKα increased proliferation rate and markedly increased cell invasiveness correlating with increased expression of pro-migratory factor, uPa. In both cell lines, overexpression of ChKα had a positive effect on choline uptake, anchorage independent growth which was more pronounced in LNCaP than in PC-3. Thus, greater enhancements of malignant phenotypes were observed in the more differentiated LNCaP cell line.

Conclusions Differential effects were observed in PC-3 and LNCaP cells lines in response to ChKα overexpression. The results suggest that increased choline kinase expression indicated by choline-PET is important for progression of early stage, androgen-dependent prostate cancer but may confer little survival advantage in undifferentiated, late stage androgen-independent prostate cancer.

Research Support The work was funded in part by NIH (TRD: CA108620)