Targeting Metastasis Precursor Cells

Even before there is any evidence of an anthill, there are ants, scurrying around, laying the groundwork. Similarly, for many years before there are any visible signs that prostate cancer has spread to a distant site and started to grow, there are tumor cells, bustling around the bloodstream or bone marrow, doing their work silently. And this, believes Jun Luo, Ph.D., assistant professor of urology, is the best time to take action against metastasis.

“We call them ‘metastasis precursor cells,’” says Luo, the Phyllis and Brian L. Harvey Scholar, “and they are essential for the development of distant metastasis. Because they are readily accessible to drugs, we believe that if we can target these cells in men at risk of recurrence, or at the time of PSA recurrence, then we can delay or even prevent clinical metastasis.”

Luo has a novel target, called AGR2 (Anterior Gradient 2), a molecule that helps these metastasis precursor cells adapt and survive in foreign conditions (away from the original prostate tumor). It seems to bear the quality of being tenacious. “Its counterpart in the frog embryo is apparently involved in the formation of a structure the embryos use to attach to the rocks, before they become tadpoles,” notes Luo. In humans, AGR2 has not been studied much; however, recent evidence suggests that it is highly expressed in prostate cancer, and more importantly, in prostate cancer that has metastasized. “Animal studies have shown that adding the AGR2 gene to nonmetastatic cancer cells turned them into cells that metastasized.”

Luo has made AGR2-blocking antibodies, and is using them on prostate cancer cells in mice. (The cancer cells are stained with a fluorescent protein, which makes them easier to track.) “It is well known that cancer cells don’t do well when they go afloat in the blood,” says Luo. “They are vulnerable and often die, because they do not have the support of their neighboring cancer cells in their original home — the prostate. If AGR2, as we suspect, is essential for these metastasis precursor cells to survive in the harsh new environment, then drugs that block AGR2 may one day be used to prevent and cure prostate cancer metastasis.”

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