Cancer Research News
Scientists Identify Pancreatic Cancer Stem Cells
PHILADELPHIA, February 1, 2007 − Researchers at the University of
Michigan Medical Center have, for the first time, identified human
pancreatic cancer stem cells. Their work indicates that these cells are
likely responsible for the aggressive tumor growth, progression, and
metastasis that define this deadly cancer.
In the February 1 issue of Cancer Research, the researchers demonstrate
that only 100 of these stem cells are needed to produce human pancreatic
cancer in half of mice tested. They also found these cells are at least
100 times more tumorigenic than cancer cells that did not have one of
three protein markers they believe to be associated with pancreatic
cancer stem cells.
The findings could help advance development of new therapies for this
cancer, which has a five-year survival rate of only three percent − the
worst prognosis of any major cancer, said the study’s lead author, Diane
M. Simeone, M.D., an associate professor of surgery and molecular and
“The cells we isolated are quite different from 99 percent of the
millions of other cells in a human pancreatic tumor, and we think that,
based on some preliminary research, standard treatments like
chemotherapy and radiation may not be touching these cells,” said
Simeone. “If that is why pancreatic cancer is so hard to treat, a new
approach might be to design a drug that specifically targets pancreatic
cancer stem cells without interfering with normal stem cell function.”
While such a drug has not been developed, ongoing research suggests it
is possible to do so, she added.
The study also advances the emerging notion that stem cells may lie at
the heart of some, if not all, cancers, Simeone said. That theory
suggests that only cells that have the properties of “stemness”− that
is, cells that can self-renew and differentiate into other types of
cells − are the only ones capable of producing tumors. These “cancer
stem cells,” could derive from normal adult stem cells in organs that
have mutated, or from a differentiated cell that has devolved to take on
the qualities of stem cells. They are resistant to traditional therapy
designed for cells that rapidly turn over because stem cells don’t,
according to some researchers. Thus, they remain after tumors shrink and
may be responsible for cancer recurrence and metastasis.
This study confirms at least one of those concepts, the researchers
said. “Our study demonstrates that the very small subset of cells in a
human pancreatic tumor that cause the cancer to grow and propagate have
stem cell-like features,” Simeone said.
To look for cancer stem cells in pancreatic cancer, the research team
implanted cancerous tissue from human pancreatic specimens removed
during patient surgery in “xenograft” mice with compromised immune
systems. Researchers removed tumors after they grew, and then sorted
millions of cancer cells to isolate those that had one or more of three
surface protein markers − CD44, CD24, and ESA. They chose these markers,
called cell adhesion molecules, because they’d recently been found on
isolated breast cancer cells by study co-authors Max Wicha, M.D., from
Michigan and Michael Clarke, Ph.D., from Stanford University School of
The researchers then implanted about 100 of each type of cell in mice,
and found that tumors would grow in a subset of the animals, but cells
that expressed all three markers were the most potent, producing tumors
in six of 12 mice tested. If more cells are used, “we can get tumors to
grow 100 percent of the time,” Simeone said. “These cells are highly
tumorigenic, which reflects the biology of this cancer.”
Additionally, the tumors derived from the highly tumorigenic pancreatic
cancer cells “appeared remarkably similar to the appearance of tumors
taken directly from patients,” Simeone said. The purported cancer stem
cells produced a diverse mixture of cells, some of which are not
cancerous, that reflected an actual human pancreatic tumor, she said.
The markers that define the highly aggressive pancreatic cancer subtype
are not identically matched to those found in aggressive breast cancer,
the researchers also discovered. The difference is in one marker, CD24,
which is negative in breast cancer and positive in pancreatic cancer,
according to Simeone.
“These studies suggest that several stem cell markers may be shared by
cancer stem cells in different tumor types, such as CD44 and CD133, but
it is possible that each tumor cancer stem cell has its own set of
unique markers,” Simeone said.
The study was funded by the
Lustgarten Foundation, the Els Pardee Foundation, the Michgan Life
Sciences Corridor, and the American Diabetes Association.
Source: American Association for Cancer Research