This made Tang and colleagues wonder whether the two cell types fundamentally differ from each other and so play different roles in prostate cancer progression.
They analyzed 20 untreated prostate cancer samples staged at varying degrees of aggressiveness on the Gleason scale and 23 samples where treatment had failed. High-PSA tumor cells composed on average about 80 percent of the Gleason 7 tumors, about 60 percent of the higher grade Gleason 9/10 tumors but only about 15 percent of the treatment-failed tumors.
A database analysis of gene expression in prostate cancer was consistent with the tumor experiments, indicating an association between low levels of PSA in tumors and disease recurrence, spread to lymph nodes, metastasis and shortened patient survival.
Turning high-PSA cells green
The next challenge was separating the two cell types to understand their biological, tumor-initiating and drug-response properties.
Tang and colleagues developed a lentiviral delivery system equipped with a PSA promoter that triggers green fluorescence protein when PSA is expressed in an infected cell.
This lentiviral reporter system allowed separation of low-PSA and high-PSA cells for the first time, Tang said. A series of experiments uncovered striking differences between them.
High-PSA prostate cancer cells:
Low-PSA prostate cancer cells:
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center