Featured Research

from universities, journals, and other organizations

Level of tumor protein indicates chances cancer will spread

Date:
February 2, 2011
Source:
NIH/National Institute of Child Health and Human Development
Summary:
Researchers have discovered that high levels of a particular protein in cancer cells are a reliable indicator that a cancer will spread.

Researchers at the National Institutes of Health and the University of Hong Kong have discovered that high levels of a particular protein in cancer cells are a reliable indicator that a cancer will spread.

Related Articles


By measuring the protein's genetic material in tumors that had been surgically removed from patients, along with measuring the genetic material from surrounding tissue, the researchers could predict at least 90 percent of the time whether a cancer would spread within two years.

The findings raise the long term possibilities of new tests to gauge the likelihood that a cancer will spread and, ultimately, of a treatment that could prevent cancer from spreading.

The protein, known as CPE-delta N, is a form of carboxypeptidase E (CPE). Ordinarily, CPE is involved in processing insulin and other hormones. CPE-delta N, a variant of CPE, was present in high amounts in tumors that had spread and, to a much lesser degree, in surrounding tissues.

Cancer cells can break away from a primary tumor and spread, or metastasize, to other parts of the body, where they form new tumors. Metastatic cancer is often fatal, and health care practitioners seek to contain cancer early, before it can metastasize.

"Testing for CPE-delta N, if combined with existing diagnostic methods, offers the possibility of more accurately estimating the chances that a cancer will spread," said Alan E. Guttmacher, M.D., director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, which supported the study. "Conceivably, a patient's CPE-delta N levels could be a key guide in individualizing their cancer care to improve outcome."

The researchers estimated the likelihood of metastasis in tumor samples and tissues from patients with liver cancer and two rare tumors, pheochromocytoma and paraganglioma. They found that tumor samples from patients whose cancers had later metastasized had elevated levels of CPE-delta N.

Tests indicating high levels of the protein predicted the spread of a cancerous tumor even when conventional staging -- diagnostic techniques to gauge the extent and seriousness of a cancer -- indicated that spread was unlikely. The finding raises the possibility that testing for CPE-delta N might be used in combination with conventional staging to further refine treatment. For example, if conventional staging indicated that a cancer was unlikely to spread, but a patient's tumor had high CPE-delta N levels, that patient might be referred for more intensive therapies normally reserved for higher stage cancers.

The study's senior authors were Y. Peng Loh of NICHD's Section on Cellular Neurobiology and Ronnie Poon from the University of Hong Kong. Other authors were from the NICHD, University of Hong Kong, the Lawson Health Research Institute in Ontario, Canada; the NIH's National Cancer Institute (NCI); and the Warren Grant Magnuson Clinical Center at NIH. The research was supported in part by NICHD, NCI, The University of Hong Kong and by the Canadian government.

The findings appear in the Journal of Clinical Investigation.

The researchers tested for CPE-delta N indirectly, by measuring levels of a molecule that assists in manufacturing the protein. RNA (ribonucleic acid) works with the information in a gene to make a particular protein -- in this case, CPE-delta N.

In an analysis of tissue from 99 patients with liver cancer, the researchers compared the amount of CPE-delta N RNA from the patients' tumors with the RNA levels in surrounding tissue.

The researchers found that when the level of CPE delta-N RNA in tumors was more than twice that in the surrounding tissue, the cancer was highly likely to return or to metastasize within two years. At or below this threshold level, the cancer was much less likely to recur. Using this threshold measure, the researchers accurately predicted metastasis or recurrence in more than 90 percent of cases. Conversely, their predictions that tumors would not return in the two-year period were accurate 76 percent of the time.

Next, the researchers measured CPE-delta N RNA levels from stored tumor tissue originally removed from 14 patients with pheochromocytoma, a rare tumor of the adrenal glands, and paraganglioma, a rare tumor primarily occurring in the adrenals but sometimes in other parts of the body. Because the adrenal glands are very small, tissue surrounding the tumor was not obtainable, so the researchers measured the amount of CPE-delta N RNA in the tumor tissue only. The number of copies ranged from 150,000 to 15 million per 200 micrograms of tissue. In all of the cases where cancer was found to have recurred or metastasized, CPE-delta N RNA levels were greater than 1 million. The researchers found no metastasis or recurrence in cases in which tumors had less than 250,000 copies. Patients' status was tracked for up to eight years.

In addition, the researchers examined cells from liver, breast, colon, and head and neck, tumors and found that those known to spread most aggressively had the highest levels of CPE-delta N RNA.

The researchers next tested a potential strategy for preventing the spread of cancer by halting the production of CPE-delta N in two different mouse models. The strategy involved treating metastatic tumors with antisense RNA, which binds to RNA, preventing it from making a protein.

In the first experimental model, the researchers transplanted highly metastatic liver cancer cells beneath the skin of mice. Half the transplants were first treated with antisense RNA specific for CPE-delta N, the other half were not. After 30 days, the tumors in the mice not treated with antisense RNA for CPE-delta N were much larger than the treated tumors in the remaining mice. Next, the researchers removed the tumors from the first set of mice and transplanted them into the livers of a second group of mice. After 35 days, only the untreated tumors had spread and formed new tumors.

Dr. Loh explained that the method used in the study might some day be used to treat cancers in human beings. Currently, there are no means to deliver the antisense RNA to tumor cells. A potential approach might involve modifying a virus to carry the antisense RNA into cells.

Similarly, further research might lead to the development of drugs or other measures to block CPE-delta N and so prevent cancer from spreading.


Story Source:

The above story is based on materials provided by NIH/National Institute of Child Health and Human Development. Note: Materials may be edited for content and length.


Journal Reference:

  1. Terence K. Lee, Saravana R.K. Murthy, Niamh X. Cawley, Savita Dhanvantari, Stephen M. Hewitt, Hong Lou, Tracy Lau, Stephanie Ma, Thanh Huynh, Robert A. Wesley, Irene O. Ng, Karel Pacak, Ronnie T. Poon, Y. Peng Loh. An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers. Journal of Clinical Investigation, 2011; DOI: 10.1172/JCI40433

Cite This Page:

NIH/National Institute of Child Health and Human Development. "Level of tumor protein indicates chances cancer will spread." ScienceDaily. ScienceDaily, 2 February 2011. <www.sciencedaily.com/releases/2011/02/110201122218.htm>.
NIH/National Institute of Child Health and Human Development. (2011, February 2). Level of tumor protein indicates chances cancer will spread. ScienceDaily. Retrieved March 31, 2015 from www.sciencedaily.com/releases/2011/02/110201122218.htm
NIH/National Institute of Child Health and Human Development. "Level of tumor protein indicates chances cancer will spread." ScienceDaily. www.sciencedaily.com/releases/2011/02/110201122218.htm (accessed March 31, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, March 31, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Solitair Device Aims to Takes Guesswork out of Sun Safety

Solitair Device Aims to Takes Guesswork out of Sun Safety

Reuters - Innovations Video Online (Mar. 31, 2015) — The Solitair device aims to take the confusion out of how much sunlight we should expose our skin to. Small enough to be worn as a tie or hair clip, it monitors the user&apos;s sun exposure by taking into account their skin pigment, location and schedule. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Soda, Salt and Sugar: The Next Generation of Taxes

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015) — Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline. Video provided by Washington Post
Powered by NewsLook.com
UnitedHealth Buys Catamaran

UnitedHealth Buys Catamaran

Reuters - Business Video Online (Mar. 30, 2015) — The $12.8 billion merger will combine the U.S.&apos; third and fourth largest pharmacy benefit managers. Analysts say smaller PBMs could also merge. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) — Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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