Science Editor

Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Breast cancer is the most common malignancy suffered by American women. It accounts for more than 40,000 deaths each year. Of all the neoplastic cells in human mammary cancers, only a small minority - perhaps as few as one cell in 100 - seems capable of forming new malignant tumors, according to newly published findings in the Proceedings of the National Academy of Sciences, released online Feb. 24, 2003.

The report, co-authored by scientists at the University of Michigan in Ann Arbor, is titled: "Prospective identification of tumorigenic breast cancer cells." Its senior author is cancer biologist Michael Clarke, a professor of internal medicine at the university.

"These tumor-inducing cells have many of the properties of stem cells," Clarke observed. "They make copies of themselves by self-renewal," he added, "and produce all the other kinds of cells in the original tumor. Although similar cells have been identified in human leukemias," Clarke pointed out, "these are the first to be found in solid tumors. The cells were isolated from primary or metastatic breast cancers removed from nine women treated at UM's Comprehensive Cancer Center [CCC]."

Oncologist Max Wicha, CCC's director and a co-author of the PNAS paper, said, "The discovery may also explain why current treatments for metastatic breast cancer often fail. The goal of all our existing therapies," he continued, "has been to kill as many cells within the tumor as possible. This PNAS study suggests that the current model may not be getting us anywhere, because we have been targeting the wrong cells with the wrong treatments. Instead, we need to develop drugs targeted at eliminating the tumor's stem cells.

"For the first time," Wicha added, "we can define the important cells that determine whether the cancer will come back or be cured. Before this, we didn't even know there were such cells."

The article's first author, post-doctoral fellow Muhammad Al-Hajii, recounted how "we used specific antibodies to segregate the heterogenous cancer cells within a tumor into isolated populations. Then we injected these human cells into immune-deficient mice, and examined them every week for tumor growth for up to six months."

The team found that a small group of cells - with a phenotype common to all but one of the human tumors - could form new cancers in the mice. These cells all expressed a protein marker called CD44. In addition, they displayed very low levels, or none at all, of a different marker, CD24. To verify these results, they repeated the experiment four times.

Clarke noted, "As few as 100 to 200 of these tumor-inducing cells, isolated from eight of nine human tumors in the study, easily formed tumors in the mice, while tens of thousands of the other cancer cells from the original tumor failed to do so. Tumor cells with this particular surface marker pattern produced a new tumor in the next mouse generation every time."

He and Wicha believe it likely that similar cells drive the development of other cancer types as well. UM's CCC is establishing a new research program to identify stem cells in other malignancies, and develop new therapies to destroy them.

"This is not a cure for cancer," Clarke emphasized, "but a very promising lead, which will focus our efforts to try to find that cure."

Some Tongue-Dwelling Bacterial Species Cause Halitosis; Other Bugs, Sweet-Smelling Breath

"Your best friend won't tell you" used to be the slogan for a brand of toothpaste that masked bad breath - halitosis. It's long been known that stale or foul-smelling exhalation is caused by oral bacteria. Now researchers at the Forsyth Institute in Boston report that certain bacteria living on the tongue are guilty of halitosis, other microbes blessed with fresh-smelling breath.

Their report appears in the current Journal of Clinical Microbiology, released online Feb. 7, 2003, under the title: "Diversity of bacterial populations on the tongue dorsa of patients with halitosis and healthy patients."

The researchers compared lingual flora of individuals with halitosis and those with agreeable breath. In six participants afflicted with halitosis, they found several species not occurring in those with fresh breath. Conversely, in five subjects with fresh breath, they identified bacteria not generally found in those with offensive inhalation.

While not all samples taken from halitosis sufferers had the same bacterial makeup, the authors report that Streptococcus salivarius, Rothia mucilaginosa and a previously unidentified strain of Eubacterium were the most prevalent species on the tongues of individuals with fresh breath. The most prevalent single bacterium found in such fortunate people - S. salivarius - lurked on the tongue in only one of the individuals with malodorous breath.