Two types of prostate cells -- basal and luminal -- can give rise to cancer in mice, offering new insight into origins of the disease itself and new targets for prevention and treatment, said Baylor College of Medicine researchers in a report that appears online in the journal Cancer Cell.

"Some people would think that cancer would normally arise from the basal cells, but the idea that they can also come from luminal cells was more surprising," said Dr. Michael Ittmann, professor of pathology and immunology at BCM and a member of the faculty of the Dan L Duncan Cancer Center at the College. "Dr. Li Xin (assistant professor of molecular and cellular biology at BCM) did some elegant cell lineage tracing in studies with mice to determine this."

Basal cells give rise to the different kinds of cells found in the prostate gland. These are the differentiated cells that carry out the tasks of the prostate. Some basal cells are considered progenitor cells that are self-sustaining. Luminal cells are more differentiated, but they can also be self sustaining. They carry out secretory functions and make prostate specific antigen.

"Prostate basal cells are less susceptible than luminal cells to direct transformation into cancer cells," said Xin. Instead, the basal cells must receive an oncogenic or cancer-causing cell signal that induces them to become luminal cells, which then can undergo cancerous change.

"That is surprising also because normally more differentiated cells are resistant to carcinogenic (cancerous) change," said Ittmann. "This ultimately may have implications for therapy. The target of treatment may be different for cancers that arise directly from luminal cells than for cancer that start with basal cells."

"Suppressing the signaling pathways that induce basal-luminal differentiation might provide an efficient approach to preventing prostate cancer initiation," said Xin.

Ittmann cautioned that while the cancers arising from the different cells types differ in mice, it is not clear that there are similar differences in human cancers.

"Ultimately, you start out using the mouse model to dissect out the best treatment pathways," said Ittmann.

Others who took part in this research include Nahyun Choi and Boyu Zhang (both first authors) and Li Zhang, all of BCM.

Funding for this work came from the National Institutes of Health.