First cellular origins of prostate cancer identified
MedWire News: US researchers have discovered which type of prostate cell is responsible for starting the growth and development of prostate cancer, offering possibilities for improved predictive and diagnostic tools.
Until now, prostatic luminal cells were thought to be responsible for the development of cancer because they appear similar in shape to prostate tumor cells when viewed under a microscope.
However, Owen Witte (Howard Hughes Medical Center, Los Angeles, California) and team transplanted luminal and basal cells from healthy human prostate tissue into immunodeficient mice, and found that it was the basal and not the luminal cells that underwent the genetic changes required to develop into cancer.
"We were able to start with a basal cell and induce human prostate cancer," said Witte.
"As we go forward, this gives us a place to look in understanding the sequence of genetic events that initiates prostate cancer and defining the cell signaling pathways that may be at work fueling the malignancy, helping us to potentially uncover new targets for therapy," Witte adds.
As reported in the journal Science, the team separated basal and luminal cells from healthy prostate tissue using a cell surface marker. They introduced a virus carrying the AKT (protein kinase B), ERG (Ets-related gene), and AR (androgen receptor) genes, known to promote prostate cancer, and grafted the transformed cells onto mice.
After 16 weeks, none of the luminal cell grafts had formed tumors. However, the basal cell grafts exhibited the histological and molecular features of prostate cancer, including loss of the basal layer and expression of prostate-specific antigen.
Loss of the basal layer is a defining feature used by pathologists to diagnose cancer, Witte et al explain, and is also the feature that makes basal cells resemble luminal cells under the microscope.
"In our experimental model, basal cells show the ability to form the disease that looks like what we see in humans," said co-author Andrew Goldstein (University of California at Los Angeles).
"We conclude that basal cells may be a source of the disease in humans," he added.
The research team believes that the human-in-mouse model system used in this study could be used to determine the effectiveness of emerging cancer therapies.
"By starting with healthy cells and turning them into cancer, we can study the cancer development process," said Goldstein.
"If we understand where the cancer comes from, we may be able to develop better predictive and diagnostic tools."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
By Sarah Guy