Low-PSA tumors have long-term tumor-generating capacity
When the team implanted the two cell types in hormonally intact male mice, the rapidly reproducing PSA-positive cells caused faster growth and larger tumors in the first generation. However, after that the low-PSA cells generated larger, faster-growing tumors and tumor incidence in the high-PSA cells dropped. In fact, the low-PSA prostate cancer cells possess indefinite tumor-propagating capacity.
In contrast, when implanted in the castrated mice, the low-PSA prostate cancer cells developed much larger tumors than the corresponding high-PSA cells. In another experiment, mice with tumors generated by either cell type were then castrated and treated with hormonal therapy. Low-PSA tumors grew better in these doubly androgen-deprived mice than the high-PSA tumors.
"These findings closely resemble progression observed in patients after androgen-deprivation treatment and reflect reducedPSA-producing cells in patient tumors after androgen depletion," Tang said.
Effect of low-PSA cells in human tumors
Tang and colleagues analyzed tumor cell PSA expression in 556 human tumors and found low protein levels correlated with reduced overall survival.
They separated the two types of cells in three primary human tumors and found that low-PSA cells did not express androgen receptor and have higher cell-generating and sphere-forming capabilities than high-PSA cells.
Future research will focus on developing therapeutic targets for low-PSA cells and illuminating the epigenetic landscapes of b
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center