CONTACT: JENNIFER BROWN
Iowa City IA 52242
(319) 335-9917; fax(319) 384-4638
Release: Nov. 14, 2002
Study Suggests Tetracycline May Help Prevent Cancer Recurrence
Building on previous research, University of Iowa scientists have discovered
that a drug already being tested as an anti-cancer agent could potentially
be used in conjunction with other cancer therapies to reduce the likelihood
of cancer recurrence by targeting the tumor microenvironment.
UI scientists in the laboratory of Mary Hendrix, Ph.D., the Kate Daum Research
Professor and head of anatomy and cell biology, previously discovered that
aggressive tumor cells can modify their local environment and can induce less
aggressive tumor cells encountering this modified environment to become more
aggressive. This suggested that, in addition to treating tumor cells, changes
to the surrounding tissue caused by an aggressive tumor should also be treated
to reduce the likelihood of recurrence.
In a study, which appears in the November issue of the journal Molecular
Cancer Therapeutics, the UI researchers demonstrate that a chemically modified
tetracycline called COL-3 is able to prevent the altered cellular environment
from inducing less aggressive cancer cells to behave more aggressively.
In their earlier studies, the UI team discovered that aggressive melanoma
cells produce a molecule called laminin 5 gamma 2 chain and deposit it into
their local environment. Enzymes known as matrix metalloproteinases (MMPs)
breakdown the laminin molecules and the resulting fragments act as signaling
molecules. Less aggressive melanoma cells respond to these signaling fragments
and become more aggressive. The fragments of laminin laid down in the environment
by the aggressive tumor cells persist in the environment long after the aggressive
cells have gone and affect the less aggressive tumor cells that move into
the altered environment.
"Standard cancer treatments aim to remove or destroy aggressive cancer
cells," said Richard Seftor, Ph.D., lead author of the study and a UI
research scientist in Hendrix's lab. "However, we also need to be concerned
by the environment left behind by the aggressive cells. We may also need to
block these environmental cues."
Chemically modified tetracyclines such as COL-3, are a group of drugs derived
from the antibiotic tetracycline that, due to the chemical modification, no
longer act as antibiotics. These drugs are powerful inhibitors of MMP enzymes.
The research team found that COL-3, blocks the breakdown of laminin to the
signaling fragment. It also prevents less aggressive cells from making the
laminin molecule in the first place. Additionally, the drug inhibits a process
known as vasculogenic mimicry in aggressive melanoma cells. This process is
a hallmark of aggressive cancers.
The study results suggest that COL-3 and other drugs like it could be useful
in blocking molecular cues residing in tissue surrounding a tumor, and they
could be used in conjunction with therapies aimed at destroying aggressive
The study also found that COL-3 was able to reduce the expression of genes
associated with vasculogenic mimicry. These results raise the possibility
that this drug may be able to suppress this process in aggressive tumor cells,
which might reduce the aggressive nature of certain cancer cells.
"These studies provide clear evidence of a successful strategic approach
in modifying the tumor microenvironment that may have profound implications
in the long term management of cancer," said Hendrix, who also is deputy
director of the Holden Comprehensive Cancer Center at UI.
In addition to Hendrix and Seftor, UI researchers involved in the study
included Elisabeth Seftor, senior research specialist, and Dawn Kirschmann,
Ph.D., assistant research scientist. The study was funded by grants from the
National Cancer Institute.
The Holden Comprehensive Cancer Center is Iowa's only National Cancer Institute-designated
comprehensive cancer center. NCI-designated comprehensive cancer centers are
recognized as the leaders in developing new approaches to cancer prevention
and cancer care, conducting leading edge research and educating the public
about cancer. Visit the center online at http://www.uihealthcare.com/depts/cancercenter.
University of Iowa Health Care describes the partnership between the
UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics
and the patient care, medical education and research programs and services
they provide. Visit UI Health Care online at www.uihealthcare.com.