Johns Hopkins Kimmel Cancer Center scientists have
refined methods used in a previous study
to reveal rare pancreatic tumor stem cells thought to fuel
cancer growth and predict shortened
survival. Pancreatic cancer remains one of the deadliest
cancers and most difficult to treat.
To sift away mature cancer cells from the rarer stem
cell versions, the Johns Hopkins
scientists applied two filters to human pancreatic tumors
transplanted into mice. One filter was first
used by University of Michigan researchers to catch cells
marked with protein flags called CD44 and
CD24. The next filter screened for cells containing high
levels of an enzyme called aldehyde
dehydrogenase, also found in normal bone marrow stem cells.
The Johns Hopkins scientists previously
used the enzyme filter to identify stem cells in multiple
myeloma, a cancer of the bone marrow.
The investigators say that using both filters resulted
in a stem cell population that was two to
10 times more concentrated than using either filter alone.
Only about one in 500 pancreatic cancer
cells has stem cell features.
"Purifying this stem cell population even further is
key to identifying the ultimate pancreatic
cancer stem cell and eventually identifying the processes
that control it," said William Matsui,
assistant professor of oncology in the School of Medicine.
Investigators could use the information to
create drugs that attack stem cell-specific gene products
and track stem cell populations as the drugs
take effect.
Further analysis revealed that pancreatic cancer stem
cells marked with aldehyde
dehydrogenase were found in patients who survived on
average four months less than patients whose
cells lacked the enzyme.
Cancer that spreads is the main culprit in cancer
deaths, and the Johns Hopkins researchers
believe stem cells have a role in this.
"These stem cells have physical properties similar to
the types of cells that are invasive and
likely to spread to distant sites," said Zeshaan Rasheed,
clinical fellow at the Johns Hopkins Kimmel
Cancer Center.
In addition to looking for new drug targets, the
investigators are planning studies to tease out
stem cells' role in cancer metastasis and disease
outcome.
The scientists presented their findings at the
American Association for Cancer Research
Annual Meeting, held April 12 to 16 in San Diego.
The study was funded by the National Institutes of
Health. Additional participants include Jie
Yang, Qiuju Wang, Irwin Freed, Daniel Laheru, Xiaobing He,
David Berman, Manuel Hidalgo, Antonio
Jimeno, Hansbart Koorstra, Seung-Mo Hong and Anirban
Maitra, all of Johns Hopkins.
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