Featured Research

from universities, journals, and other organizations

How tumors remodel their surroundings to grow: New study provides insight

Date:
July 3, 2014
Source:
Sanford-Burnham Medical Research Institute
Summary:
Research identifies a mechanism in the tumor stroma that triggers an inflammatory response, promoting tumor growth and metastasis. The findings suggest a new approach to anti-cancer therapies that incorporates targets in the tumor microenvironment, and contribute to the increasing acknowledgement that the cells and tissue surrounding a tumor -- the stroma -- are an integral part of cancer initiation, growth, and expansion.

A team of scientists from Sanford Burnham Medical Research Institute (Sanford-Burnham) has found that the loss of a protein called p62 in the cells and tissue surrounding a tumor can enhance the growth and progression of tumors. The study suggests that therapies targeting the tumor microenvirnoment may be as important as targeting the tumor itself.

The findings, published July 3 in Cancer Cell, contribute to the increasing acknowledgement that the cells and tissue surrounding a tumor -- the stroma -- are an integral part of cancer initiation, growth, and expansion.

"Our study reveals a precise mechanism that stromal cells use to encourage the tumorigenesis of epithelial cancer cells," said Jorge Moscat, Ph.D., director of the Cell Death and Survival Networks Program at Sanford-Burnham. "We have shown that in the stroma, p62 acts as an anti-inflammatory tumor suppressor, controlling the inflammatory environment and the signals that promote cancer. In the absence of p62, tumors grow larger and are more inclined to metastasize."

p62 location influences tumor growth

Previously, Moscat and colleagues demonstrated that p62 activation in prostate and lung cancer epithelial cells had tumor-promoting effects. Cancers of the epithelial cells are called carcinomas, and about 85 percent of all cancers are carcinomas.

In the current study, his team studied the effects of p62 in the tissue adjacent to the tumor, and found it had the reverse effects there.

"These are highly significant observations since p62 activates another protein called mTOR which is a biological target of many ongoing clinical trials in cancer right now," said Maria Diaz-Meco, Ph.D., professor at Sanford-Burnham and co-author of the study.

"This potentially means that therapeutic strategies aimed at depleting an organism of p62 and inhibiting mTOR in the cells that surround the tumor may actually benefit the tumor, because tumor-suppressive activities would be inactivated. It also may explain why therapies aimed at blocking mTOR are showing limited clinical efficacy," added Diaz-Meco.

Unveiling the mechanism of p62

The initial hint that p62 in the stroma influences tumor growth came by analyzing more than 200 human prostate tumors with Gleason scores ranging from 2 to 10. Gleason scores are a numerical assignment given to prostate tumors based on pathology, with the highest scores (10 maximum) indicating that the cancer is very likely to spread. The research team found that p62 levels in the stroma were significantly lower in samples with the highest Gleason scores, suggesting a protective role for p62.

To understand how p62 works, the research team introduced prostate cancer cells and monitored tumor formation in normal mice, and mice genetically engineered to lack p62. The mice without p62, called p62 knockout (KO) mice, had larger prostate tumors compared to normal mice, supporting the notion that the absence of p62 in an organism promotes cancer growth.

The researchers went on to show that p62 KO mice had increased levels of IL-6, a pro-inflammatory cytokine (a signaling molecule) that enhances tumor cell proliferation and inhibits cell death. And, the genetic events that linked p62 depletion to increased levels of IL-6 in mice were mirrored in humans.

"Our observations support a more comprehensive approach to treating cancer, one that is based on our understanding of the communications between a tumor and its environment," added Moscat. "Conceivably, treatments that inhibit tumor-promoting inflammatory signals combined with tumor-specific targets may improve cancer outcomes."


Story Source:

The above story is based on materials provided by Sanford-Burnham Medical Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Tania Valencia, JiYoung Kim, Shadi Abu-Baker, Jorge Moscat-Pardos, ChristopherS. Ahn, Miguel Reina-Campos, Angeles Duran, EliasA. Castilla, ChristianM. Metallo, MariaT. Diaz-Meco, Jorge Moscat. Metabolic Reprogramming of Stromal Fibroblasts through p62-mTORC1 Signaling Promotes Inflammation and Tumorigenesis. Cancer Cell, 2014; DOI: 10.1016/j.ccr.2014.05.004

Cite This Page:

Sanford-Burnham Medical Research Institute. "How tumors remodel their surroundings to grow: New study provides insight." ScienceDaily. ScienceDaily, 3 July 2014. <www.sciencedaily.com/releases/2014/07/140703125212.htm>.
Sanford-Burnham Medical Research Institute. (2014, July 3). How tumors remodel their surroundings to grow: New study provides insight. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2014/07/140703125212.htm
Sanford-Burnham Medical Research Institute. "How tumors remodel their surroundings to grow: New study provides insight." ScienceDaily. www.sciencedaily.com/releases/2014/07/140703125212.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
Powered by NewsLook.com
House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Uganda on Alert for Ebola but No Confirmed Cases

Uganda on Alert for Ebola but No Confirmed Cases

AFP (July 31, 2014) Uganda's health minister said on Thursday that there are no confirmed cases of Ebola in the country, but that it remained on alert for cases of the deadly virus. Uganda has suffered Ebola outbreaks in the past, most recently in 2012. Duration: 00:59 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:
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