Featured Research

from universities, journals, and other organizations

Clues To Prevent Spread Of Ovarian Cancer

Date:
March 18, 2008
Source:
University of Chicago Medical Center
Summary:
A drug that blocks production of an enzyme that enables ovarian cancer to gain a foothold in a new site can slow the spread of the disease and prolong survival in mice, but only if the drug is given early in the disease process.

A drug that blocks production of an enzyme that enables ovarian cancer to gain a foothold in a new site can slow the spread of the disease and prolong survival in mice, according to a study by researchers from the University of Chicago Medical Center, but only if the drug is given early in the disease process.

In the April issue of the Journal of Clinical Investigation, the researchers show that an enzyme known as MMP-2 is necessary for ovarian cancer to attach itself to the sites where it tends to spread. Several drugs known as MMP inhibitors (for example, marimastat or prinomastat) inhibit the enzyme, dramatically reducing the tumor's ability to establish itself at sites beyond the ovary. But such MMP inhibitors, which were abandoned after they failed to extend survival in earlier clinical trials, have to be given before the cancer has spread.

"Our study suggests that MMP-2 inhibitors could have a significant impact on ovarian cancer but only if administered quite early, before the cancer has advanced beyond the ovary," said Ernst Lengyel, assistant professor of obstetrics and gynecology at the University of Chicago.

This approach could help women who receive surgical treatment while the disease is still limited to the ovary as well as those who have successful surgery to remove all evidence of local spread of the disease. In the earlier trial, marimastat was given to women with late-stage disease that had already spread.

The fifth leading cause of cancer death in women, ovarian cancer -- unlike breast, colon or lung cancer -- tends to spread within the abdominal cavity and not to distant organs. Carried by fluid, it most often spreads throughout the peritoneal cavity and to the omentum, a large fat pad draped over the small bowel.

Lengyel and colleagues wanted to understand the many steps required for ovarian cancer to dislodge from its original site and establish itself elsewhere in the peritoneal cavity. They found that one of the key steps was production of MMP-2 by cancer cells that came in contact with the cells that line the peritoneal cavity.

When ovarian cancer cells make contact with the cells that line this internal cavity, they produce MMP-2 (an acronym for matrix metalloproteinase-2). MMP-2 alters two proteins--vitronectin and fibronectin--found on the surface of the cells that line the cavity. These alterations change those proteins in a way that enables the cancer cells to latch on to them better. Once attached, the cancer cells can multiply rapidly and invade.

By inhibiting MMP-2 activity early in the disease course, Lengyel and colleagues were able to prevent injected ovarian cancer cells from attaching to their target tissues in the peritoneum and omentum. This reduced the growth of new tumors by 68 percent, when measured four weeks after treatment.

The inhibitor nearly doubled survival time in mice that were injected with ovarian cancer cells. Those who received it survived an average of 63 days, compared to untreated mice, who survived only 36 days.

Brief and early intraperitoneal treatment with an MMP inhibitor, the authors conclude, may reduce peritoneal attachment, reduce metastases and significantly prolong survival.

The treatment has much less impact, however, once cancerous cells have attached and formed colonies. In several earlier trials, marimastat, an oral MMP inhibitor, was given for a prolonged period of time to women with late-stage disease that had already spread.

"MMP-inhibitors were given at the wrong time for too long, causing side effects," Lengyel said. Attachment is the first step for metastatic spread. MMP-2, the target of MMP inhibitors, plays a role in early cancer spread.

"Our study examines the initial step of ovarian cancer metastasis," the authors note, when cancer cells meet unprepared target cells. Other steps in this process, they suggest, may also provide additional treatment targets.

The National Institutes of Health, the Department of Defense, the Ovarian Cancer Research Fund, the Gynecologic Cancer Foundation and the Illinois Department of Health funded the research. Additional authors include Hilary Kenny and Swayamjot Kaur of the University of Chicago and Lisa Coussens of the University of California San Francisco.


Story Source:

The above story is based on materials provided by University of Chicago Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University of Chicago Medical Center. "Clues To Prevent Spread Of Ovarian Cancer." ScienceDaily. ScienceDaily, 18 March 2008. <www.sciencedaily.com/releases/2008/03/080313185738.htm>.
University of Chicago Medical Center. (2008, March 18). Clues To Prevent Spread Of Ovarian Cancer. ScienceDaily. Retrieved September 1, 2014 from www.sciencedaily.com/releases/2008/03/080313185738.htm
University of Chicago Medical Center. "Clues To Prevent Spread Of Ovarian Cancer." ScienceDaily. www.sciencedaily.com/releases/2008/03/080313185738.htm (accessed September 1, 2014).

Share This




More Health & Medicine News

Monday, September 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
New Drug Could Reduce Cardiovascular Deaths

New Drug Could Reduce Cardiovascular Deaths

Newsy (Aug. 30, 2014) The new drug from Novartis could reduce cardiovascular deaths by 20 percent compared to other similar drugs. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins