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Prostate Cancer Stem Cells Emerge from Low-PSA Cells

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While discussion continues over the value of screening healthy men for prostate cancer by testing for levels of prostate specific antigen (PSA) in their blood, scientists have found another use for PSA.

Prostate cancer cells that express low levels of the protein give rise to cancer stem cells that are both hard to kill with existing drugs and highly capable of generating cancer cells on a large scale.

A team of scientists led by MD Anderson's Dean Tang, Ph.D., professor in MD Anderson's Department of Molecular Carcinogenesis, reports its findings about low-PSA prostate cancer cells today in the May edition of Cell Stem Cell.

"Using a new technique, we were able for the first time to separate low-PSA and high-PSA prostate cancer cells, which led to the discovery of a low-PSA population of cancer stem cells that appears to be an important source of castration-resistant prostate cancer," says Tang.



Hormone therapy is used to block production of testosterone, which fuels prostate cancer growth, by either chemical or physical castration. Tumors eventually become resistant to this approach.

Separating the two types of cell revealed striking, important differences.

High-PSA prostate cancer cells:
  • Divide rapidly, making them vulnerable to chemotherapy that targets fast-proliferating cells.
  • Express high levels of the androgen receptor, a key to testosterone production, and so are vulnerable to hormonal therapy. 
  • Produce only identical copies of themselves when they divide.
Low-PSA prostate cancer cells:
  • Divide slowly and express anti-stress genes that help them resist chemotherapy.
  • Either lack or have a weak presence of the androgen receptor, allowing them to grow while hormonal therapy wipes out PSA-positive cells.
  • Are capable of dividing into one copy of themselves and one PSA-positive cell during reproduction. The researchers captured this on video microscopy, filming the division of a grey low-PSA cell into one copy of itself and one copy of a vibrantly green PSA-positive cell.

This last feature is called asymmetric cell division. "Asymmetric cell division is the gold standard feature of normal stem cells," Tang said. The team's video of this cell division in action confirms the lab findings. 

Cell division videos
In the video above, we first see a grey low-PSA prostate cancer stem cell that slowly divides into a copy of itself and a fluorescent green PSA-positive cell. Asymmetric cell division in action. the green cells are PSA-positive cells, which are seen dividing rapidly and reproducing only copies of themselves.

In the video below, the green cells are PSA-positive cells, which are seen dividing rapidly and reproducing only copies of themselves.

Videos are courtesy of Tang et al, Cell Stem Cell, Volume 10, Issue 5.



The team analyzed 43 human prostate cancer tumors and found a higher proportion of low-PSA cells in more advanced tumors. They also analyzed PSA expression in 556 human tumors and found low PSA expression associated with shorter overall survival.

Tang's lab is focusing on development of new therapeutics to target low-PSA prostate cancer cells that can be combined with hormone therapy to wipe out cancer cells and prevent recurrence

Additional information

MD Anderson news release

 

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