A Tale of Two Cells: Discovering the Origin of Prostate Cancer

Abstract

I n July, researchers in the lab of Owen Witte, M.D., at the University of California, Los Angeles, reported in Science that human prostate basal cells, transformed and then transplanted into mice, could form tumors. But in September 2009, a different group reported in Nature that prostate cancer in mice originated from a rare population of luminal cells. Basal versus luminal: irreconcilable? Apparently not. “Neither of them contradicts each other at all,” said Lynette Wilson, Ph.D., a professor in the departments of cell biology and urology at New York University. It’s possible that there are different prostate cancer cells of origin, she said. And the two papers are together a big step forward for a fi eld badly lacking such basic knowledge. That’s because the cellular origins of prostate cancer are still largely unknown. “The prostate cancer fi eld is struggling because, unlike [for] the breast, there is not a clear consensus about prostatic cell lineage,” said Gail Risbridger, Ph.D., a professor in the department of anatomy and developmental biology at Monash University in Melbourne, Australia. In breast cancer, six different subtypes have been mapped out, each arising from a distinct step in the differentiation of breast tissue from a common precursor cell. But we do not yet have such a map for prostate cancer. “This whole fi eld is still in its infancy,” Wilson said. Closing this knowledge gap could be the key to distinguishing between aggressive and indolent cancers and in developing individualized treatments — research that’s much further along in some other cancers. “It is conceivable that by identifying cell types of origin, you could distinguish different types of prostate cancer that differ in terms of their prognosis and/or treatment response,” said Michael Shen, Ph.D., a professor of medicine and genetics and development at Columbia University in New York. Shen led the group that reported in Nature last year that a rare population of luminal cells in mice gave rise to prostate cancer. That study and the recent report in Science open the door to new experiments that should pin down the exact cell types in which human prostate cancer originates.