Hello Everyone,

This has been a fruitful day for me in finding several encouraging
articles to help with cancer. Hope this may be helpful to some of
you. bg

http://www.uiowa.edu/~ournews/2002/november/1114tetracycline.html
CONTACT: JENNIFER BROWN
5137 Westlawn
Iowa City IA 52242
(319) 335-9917; fax(319) 384-4638
e-mail: brownj@...
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 tumor cells.

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.